subject:(Neurotoxicology)

Rutgers University

1. Nnodi, Oluchukwu U. Comparative neurotoxicities of amphotericin B and amphotericin B methyl ester in mice and on oligodendrocytes in culture.

Degree: PhD, Toxicology, 2014, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/45382/

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Amphotericin B methyl ester (AME) similar to Amphotericin B (AMB), is a macrolide antibiotic highly effective against complex systemic fungal infections. Clinical data suggested AME… (more)

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Amphotericin B methyl ester (AME) similar to Amphotericin B (AMB), is a macrolide antibiotic highly effective against complex systemic fungal infections. Clinical data suggested AME was neurotoxic, but subsequent analysis of lots used in its only clinical-trial revealed contamination with AMB and multi-methylated AMB-derivatives. Accruing evidence suggests AMB not highly-purified AME causes neurotoxicity, thus, it is likely that AMB contributed to neurotoxicity observed during the AME trials. Preliminary assessment of adult Balb/c mice given alternate day intraperitoneal (i.p) AME to mimic the human dose used (5 mg/kg of body weight [b.w]) compared with similarly treated AMB mice was carried out after 1-month and 2-months of injections. Light microscopy of cerebral white matter stained with hematoxylin/eosin and luxol fast blue suggested AME caused less demyelination than AMB. AMB induced CNS demyelination persisted after 3-months of drug-cessation following 2-months of injections. The nuclear area factor (NAF) analysis of AMB-brains provides preliminary data that AMB may cause apoptotic change in cerebral white matter of mice. Myelin lesions were absent in AME-brains, and even after 5-months of day i.p treatment of adult mice with 7-mg/kg b.w of AME alone, ultrastructural myelin changes were minimal. Differentiated human oligodendrocyte cell line (MO3.13) exposed to 0.5-30µg/ml AMB or AME for 24 hours demonstrated a progressive increase in cytotoxicity as determined by dye exclusion. The lowest concentration of AMB to induce cell injury was 1µg/ml, whereas injury first appeared in AME-exposed cells at10 µg/ml, a concentration far exceeding those expected in clinical use. AMB at1µg/ml showed apoptotic nuclear change in cells colocalizing for propidium iodide and fluorescein diacetate. Confirmation with Hoechst and fluorescent inhibition of caspases labeling revealed a significant decrease in the NAF and an increase in caspase-3 and -9 activity, suggesting induction of the intrinsic mitochondrial apoptotic pathway. AMB also caused increased cytochrome c release with a significant loss of mitochondrial membrane potential (ΔΨΜ) that was refractory to rescue with Trolox as determined with JC-1 dye. Cytotoxicity was not observed in similarly treated AME-cells. Our data suggests that AMB, but not AME may induce oligodendrocytes cytotoxicity and mitochondrial damage, eventually diminishing ΔΨΜ with consequent apoptosis.

Advisors/Committee Members: Reuhl, Reuhl R (chair), Robson, Mark G (internal member), Cooper, Keith R (internal member), Richardson, Jason (internal member), Borders, Donald B (outside member).

Subjects/Keywords: Amphotericin B; Neurotoxicology

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APA (6^th Edition):

Nnodi, O. U. (2014). Comparative neurotoxicities of amphotericin B and amphotericin B methyl ester in mice and on oligodendrocytes in culture. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/45382/

Chicago Manual of Style (16^th Edition):

Nnodi, Oluchukwu U. “Comparative neurotoxicities of amphotericin B and amphotericin B methyl ester in mice and on oligodendrocytes in culture.” 2014. Doctoral Dissertation, Rutgers University. Accessed January 20, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/45382/.

MLA Handbook (7^th Edition):

Nnodi, Oluchukwu U. “Comparative neurotoxicities of amphotericin B and amphotericin B methyl ester in mice and on oligodendrocytes in culture.” 2014. Web. 20 Jan 2021.

Vancouver:

Nnodi OU. Comparative neurotoxicities of amphotericin B and amphotericin B methyl ester in mice and on oligodendrocytes in culture. [Internet] [Doctoral dissertation]. Rutgers University; 2014. [cited 2021 Jan 20]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/45382/.

Council of Science Editors:

Nnodi OU. Comparative neurotoxicities of amphotericin B and amphotericin B methyl ester in mice and on oligodendrocytes in culture. [Doctoral Dissertation]. Rutgers University; 2014. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/45382/

Central Connecticut State University

2. Walsh, Christine E., 1975-. Community Water Fluoridation in the United States and the Possible Threat of Neurotoxicity to Humans.

Degree: Department of Biology, 2018, Central Connecticut State University

URL: http://content.library.ccsu.edu/u?/ccsutheses,2715

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Objective: Research the history and current practices of water fluoridation and review scientific literature on the impacts of fluoride on neurotoxicity to determine if water… (more)

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Objective: Research the history and current practices of water fluoridation and review scientific literature on the impacts of fluoride on neurotoxicity to determine if water fluoridation in the United States can credibly pose a risk to human neurodevelopment. Methods: Utilizing information obtained from the United States: CDC, EPA, NLM, and NSF, AWWA a history and current practices of water fluoridation in the United States were gathered. Utilizing PubMed and Medline databases, research studies in related topics to fluoride and neurotoxicity were analyzed and were used as background support (secondary research) or as the foundation of the main topic of neurotoxicity and cognitive development (primary research). Results: Ingestion of high amounts of fluoride has shown clinical manifestations such as dental fluorosis and in more extreme cases, skeletal fluorosis. Fluoride has been shown to affect CNS development and activity through laboratory studies but there is insufficient evidence to correlate fluoride to all types of learning and cognitive disorders due to other extraneous variables. Conclusion: If water fluoridation was a stand-alone source of fluoride consumption and 0.7 ppm could be guaranteed within the water supply, the current fluoridation level would pose minimal to no risk of neurotoxicity within the United States. Due to the many exogenous sources of fluoride available, and by the admission of the CDC that humans are ingesting between 0.6 and 6.6 mg/L (parts per million) of fluoride on a daily basis, anthropogenic water fluoridation is an act that should have serious reconsideration. While water fluoridation may have the ability to contribute to the formation of stronger enamel when ingested at an early age, it has minimal benefit to adult populations. The risk of ingesting elevated levels of fluoride from all combined sources could potentially lead to neurotoxic defects such as lowered IQ.

"Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in Biological Sciences."; Thesis advisor: Mark Jackson.; M.S.,Central Connecticut State University,,2018.;

Advisors/Committee Members: Jackson, Mark E.

Subjects/Keywords: Water – Fluoridation – United States.; Neurotoxicology.

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APA (6^th Edition):

Walsh, Christine E., 1. (2018). Community Water Fluoridation in the United States and the Possible Threat of Neurotoxicity to Humans. (Thesis). Central Connecticut State University. Retrieved from http://content.library.ccsu.edu/u?/ccsutheses,2715

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Walsh, Christine E., 1975-. “Community Water Fluoridation in the United States and the Possible Threat of Neurotoxicity to Humans.” 2018. Thesis, Central Connecticut State University. Accessed January 20, 2021. http://content.library.ccsu.edu/u?/ccsutheses,2715.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Walsh, Christine E., 1975-. “Community Water Fluoridation in the United States and the Possible Threat of Neurotoxicity to Humans.” 2018. Web. 20 Jan 2021.

Vancouver:

Walsh, Christine E. 1. Community Water Fluoridation in the United States and the Possible Threat of Neurotoxicity to Humans. [Internet] [Thesis]. Central Connecticut State University; 2018. [cited 2021 Jan 20]. Available from: http://content.library.ccsu.edu/u?/ccsutheses,2715.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Walsh, Christine E. 1. Community Water Fluoridation in the United States and the Possible Threat of Neurotoxicity to Humans. [Thesis]. Central Connecticut State University; 2018. Available from: http://content.library.ccsu.edu/u?/ccsutheses,2715

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

3. Bhatia, Inderjeet. An in vivo model of bilirubin neurotoxicity.

Degree: 2000, University of Hong Kong

URL: http://hdl.handle.net/10722/33897

Subjects/Keywords: Bilirubin.; Neurotoxicology.

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APA (6^th Edition):

Bhatia, I. (2000). An in vivo model of bilirubin neurotoxicity. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/33897

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bhatia, Inderjeet. “An in vivo model of bilirubin neurotoxicity.” 2000. Thesis, University of Hong Kong. Accessed January 20, 2021. http://hdl.handle.net/10722/33897.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bhatia, Inderjeet. “An in vivo model of bilirubin neurotoxicity.” 2000. Web. 20 Jan 2021.

Vancouver:

Bhatia I. An in vivo model of bilirubin neurotoxicity. [Internet] [Thesis]. University of Hong Kong; 2000. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10722/33897.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bhatia I. An in vivo model of bilirubin neurotoxicity. [Thesis]. University of Hong Kong; 2000. Available from: http://hdl.handle.net/10722/33897

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

California State University – Sacramento

4. Tinsley, Brendan. Determining if bisphenol-A confers risk of autism using Drosophila melanogaster as a model.

Degree: MS, Biological Science (Molecular and Cellular Biology, 2020, California State University – Sacramento

URL: http://hdl.handle.net/10211.3/216899

► Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with complex, multifactorial etiologies that are incompletely understood. Over the last decade, numerous genomic… (more)

▼ Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with complex, multifactorial etiologies that are incompletely understood. Over the last decade, numerous genomic studies have led to the identification of hundreds of genes linked to ASD, but identification of environmental factors that confer risk of ASD has lagged behind. Environmental chemicals are one class of environmental factor of concern due to 1) the limited toxicological analysis on existing chemicals, and 2) the extent to which humans come in contact with these chemicals. Bisphenol A (BPA) is a chemical used in the synthesis of plastics that is found in a wide variety of food and personal care items that humans come in contact with every day. There is extensive data showing BPA functions as an endocrine disruptor, but recent studies have indicated that it may also affect neurodevelopment. Here, I investigated the neurodevelopmental toxicity of BPA and its potential as an ASD risk factor, using Drosophila melanogaster as a model organism. Drosophila have a high degree of conservation with humans with respect to the genes and molecular pathways that govern neurodevelopment. As such, fruit flies are increasingly being used as a model of human neurodevelopmental disorders. The aim of this research was to determine if developmental exposure to BPA affects two neurodevelopmental processes relevant to ASD: axon outgrowth and neural stem cell (NSC) proliferation. Importantly, this study also addressed if the effect of BPA exposure varies in the presence of a significant ASD risk gene. To do so, wild-type Drosophila and Drosophila carrying a mutation in fragile X mental retardation 1 (fmr1)???the most common single gene cause of autism???were exposed to BPA during development and consequent axon outgrowth and NSC proliferation phenotypes were compared. Axon outgrowth was examined by imaging the mushroom body of adult flies. Data was generated from these images through scoring the degree of aberrant midline crossing by axons in this structure. This approach showed that BPA increased the severity and frequency of midline crossing in wild-type flies, but exhibited a neuroprotective effect in fmr1 flies. To assess NSC proliferation, images were taken of larval brains and the number of NSCs and intermediate neural progenitor cells (INPs) undergoing mitosis was directly counted. This analysis showed that BPA significantly decreased the number of mitotically active NSCs and INPs in wild-type flies, but not in fmr1 mutant flies. Advisors/Committee Members: Mulligan, Kimberly.

Subjects/Keywords: Neurodevelopment; Bisphenol A; Neurotoxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tinsley, B. (2020). Determining if bisphenol-A confers risk of autism using Drosophila melanogaster as a model. (Masters Thesis). California State University – Sacramento. Retrieved from http://hdl.handle.net/10211.3/216899

Chicago Manual of Style (16^th Edition):

Tinsley, Brendan. “Determining if bisphenol-A confers risk of autism using Drosophila melanogaster as a model.” 2020. Masters Thesis, California State University – Sacramento. Accessed January 20, 2021. http://hdl.handle.net/10211.3/216899.

MLA Handbook (7^th Edition):

Tinsley, Brendan. “Determining if bisphenol-A confers risk of autism using Drosophila melanogaster as a model.” 2020. Web. 20 Jan 2021.

Vancouver:

Tinsley B. Determining if bisphenol-A confers risk of autism using Drosophila melanogaster as a model. [Internet] [Masters thesis]. California State University – Sacramento; 2020. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10211.3/216899.

Council of Science Editors:

Tinsley B. Determining if bisphenol-A confers risk of autism using Drosophila melanogaster as a model. [Masters Thesis]. California State University – Sacramento; 2020. Available from: http://hdl.handle.net/10211.3/216899

University of California – San Diego

5. Hagstrom, Danielle Nicole. Establishment and Validation of the Freshwater Planarian, Dugesia japonica, as an Alternative Animal Model for Developmental Neurotoxicology using Organophosphorus Pesticides.

Degree: Biology, 2018, University of California – San Diego

URL: http://www.escholarship.org/uc/item/1vw2f0wh

► A paradigm shift has recently occurred in the field of toxicology, transitioning away from traditional mammalian models in favor of time- and cost-efficient alternatives, such… (more)

▼ A paradigm shift has recently occurred in the field of toxicology, transitioning away from traditional mammalian models in favor of time- and cost-efficient alternatives, such as in vitro systems and non-mammalian animal models, which are amenable to high-throughput screening. We have pioneered the asexual freshwater planarian, Dugesia japonica, as an alternative model for developmental neurotoxicology. Planarians have strong regenerative capabilities, wherein after decapitation, the resulting tail piece will regenerate a new head, including a brain, within 2 weeks. Moreover, planarians possess several quantifiable behaviors coordinated by distinct neuronal subpopulations, enabling testing of both adult and developing/regenerating animals with the same assays to directly compare effects on neuronal function. We have established and begun validating the planarian toxicology platform through screens testing 10-87 compounds. We demonstrate that planarians have similar sensitivity to existing alternative animal models, such as developing zebrafish. Planarians are particularly sensitive to pesticides and are good predictors of known developmentally neurotoxic pesticides, such as organophosphorus pesticides (OPs), one of the most used class of pesticides in the world. OPs are acutely toxic due to inhibition of acetylcholinesterase (AChE), leading to accumulation of acetylcholine and subsequent cholinergic overstimulation. However, growing evidence suggests that chronic, low dose exposure to OPs, particularly during development, may cause toxicity independent of effects on AChE. Alternative mechanisms of OP developmental neurotoxicity have been proposed, but direct connections between molecular/cellular defects with their functional significance have been limited using traditional models. Our planarian screening platform, on the other hand, is uniquely suited to provide the necessary link between mechanism and functional effects. First, we characterized the in vitro and in vivo properties of planarian cholinesterase and its structural and functional interactions with OPs to contextualize known OP mechanisms. Second, through a comparative screen of 6 OPs and chemicals targeting suggested alternative OP targets, including the endocannabinoid system, cytoskeleton and oxidative stress, we correlate the distinct toxicological profiles of different OPs with specific toxic pathways. Together, these studies demonstrate the utility of the planarian system to the modern toxicology pipeline, through its ability to directly connect mechanisms with their functional significance.

Subjects/Keywords: Toxicology; alternative animal models; developmental neurotoxicology; planarians

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APA (6^th Edition):

Hagstrom, D. N. (2018). Establishment and Validation of the Freshwater Planarian, Dugesia japonica, as an Alternative Animal Model for Developmental Neurotoxicology using Organophosphorus Pesticides. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/1vw2f0wh

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hagstrom, Danielle Nicole. “Establishment and Validation of the Freshwater Planarian, Dugesia japonica, as an Alternative Animal Model for Developmental Neurotoxicology using Organophosphorus Pesticides.” 2018. Thesis, University of California – San Diego. Accessed January 20, 2021. http://www.escholarship.org/uc/item/1vw2f0wh.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hagstrom, Danielle Nicole. “Establishment and Validation of the Freshwater Planarian, Dugesia japonica, as an Alternative Animal Model for Developmental Neurotoxicology using Organophosphorus Pesticides.” 2018. Web. 20 Jan 2021.

Vancouver:

Hagstrom DN. Establishment and Validation of the Freshwater Planarian, Dugesia japonica, as an Alternative Animal Model for Developmental Neurotoxicology using Organophosphorus Pesticides. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 20]. Available from: http://www.escholarship.org/uc/item/1vw2f0wh.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hagstrom DN. Establishment and Validation of the Freshwater Planarian, Dugesia japonica, as an Alternative Animal Model for Developmental Neurotoxicology using Organophosphorus Pesticides. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/1vw2f0wh

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Diego

6. Zhang, Siqi. High-throughput whole-animal screening using freshwater planarian as an alternative model for developmental neurotoxicity.

Degree: Bioengineering, 2018, University of California – San Diego

URL: http://www.escholarship.org/uc/item/9k5263nj

► The field of toxicology is under growing pressure to meet the demand of hazard assessment for the increasingly vast number of environmental toxicants. Due to… (more)

▼ The field of toxicology is under growing pressure to meet the demand of hazard assessment for the increasingly vast number of environmental toxicants. Due to low throughput and high cost, the traditional toxicity testing strategy, using rodent and higher mammalian animal-based models, is unable to adequately meet these competing demands. Hence, there is increasing recognition of the value of transforming toxicity testing to reduce the usage of mammal models and to more efficiently and reliably predict human relevant toxicity. To this end, a battery approach, integrating diverse in vitro and alternative animal models, was initiated to complement and accelerate hazard assessment. These alternative models are amenable to inexpensive, rapid and robust screening. In this dissertation, I introduce the asexual freshwater planarian Dugesia japonica as a novel alternative animal model to study developmental neurotoxicity. I developed and expanded a fully automated planarian high-throughput (HTS) screening platform to accomplish rapid screening of multiple morphological and behavioral endpoints. This HTS platform was evaluated for robustness, strengths and weaknesses, using an 87-compound library with known and suspected compounds and a 15-compound flame retardant library. As a unique advantage, the similar size of adult and regenerating planarians allows for direct comparison of two worm types to discern development-specific toxicity from overt systemic toxicity. We show that planarian is a useful model to potentially link toxicity pathways to whole-animal adverse functional outcomes by providing a large repertoire of behavioral endpoints. Comparative analysis of the planarian model with other alternative models, including zebrafish, nematode and in vitro cell-based models, provides insight into how different models complement each other in the battery approach. Finally, I discuss our comparative screen of organophosphrous pesticides (OPs) using the expanded platform, to investigate the possible mechanisms of developmental toxicity in OPs. Altogether, by establishing a new alternative animal model this work adds value to the battery approach to accelerate toxicity screening and prioritize toxicants, and provide further insight into the potential mechanisms of OP neurotoxicity.

Subjects/Keywords: Bioengineering; developmental neurotoxicology; high-throughput screening; planarian

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APA (6^th Edition):

Zhang, S. (2018). High-throughput whole-animal screening using freshwater planarian as an alternative model for developmental neurotoxicity. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/9k5263nj

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Siqi. “High-throughput whole-animal screening using freshwater planarian as an alternative model for developmental neurotoxicity.” 2018. Thesis, University of California – San Diego. Accessed January 20, 2021. http://www.escholarship.org/uc/item/9k5263nj.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Siqi. “High-throughput whole-animal screening using freshwater planarian as an alternative model for developmental neurotoxicity.” 2018. Web. 20 Jan 2021.

Vancouver:

Zhang S. High-throughput whole-animal screening using freshwater planarian as an alternative model for developmental neurotoxicity. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 20]. Available from: http://www.escholarship.org/uc/item/9k5263nj.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang S. High-throughput whole-animal screening using freshwater planarian as an alternative model for developmental neurotoxicity. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/9k5263nj

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas State University – San Marcos

7. Martinez, Melody A. Environmental Effects Of Nitrite On Goldfish (Carassius auratus) Communication.

Degree: MS, Aquatic Resources, 2020, Texas State University – San Marcos

URL: https://digital.library.txstate.edu/handle/10877/12272

► Increased agriculture and industrial activity have elevated concentrations of nitrogenous compounds in aquatic ecosystems. Exposure to elevated nitrite concentrations disrupt physiological and endocrine processes such… (more)

▼ Increased agriculture and industrial activity have elevated concentrations of nitrogenous compounds in aquatic ecosystems. Exposure to elevated nitrite concentrations disrupt physiological and endocrine processes such as ion and hormone regulation, respiratory, and cardiovascular activity. However, there is a lack of research in the effects of nitrite on sensitive organs such as the olfactory epithelium. Fish olfactory systems are highly sensitive and can detect odors in the picomolar concentration. Odorant signals are integrated in the brain and trigger vital physiological functions (e.g. reproduction and feeding) and behavior. Therefore, disruption of the olfactory system will have a cascade of effects, affecting the viability of species in the short or long term. To detect odors, this specialized sensitive organ is continuously exposed to the aquatic environment, making it highly susceptible to toxins like nitrite. We hypothesize olfactory tissue will be adversely affected by nitrite. Thus, nitrite will accumulate and structurally alter the olfactory organ, which will change behavioral responses to odors and therefore act as a neurotoxin. The goal, to determine the acute and chronic effects of nitrite and its accumulation in the olfactory system and vital organs in goldfish. To test our hypothesis, three experiments were conducted; acute nitrite exposure, chronic nitrite exposure, and behavior assessments on chronically exposed fish. Acute exposure fish were exposed to nitrite concentrations (0, 0.3, 1.0, and 10 mM) for 5 days. Chronic exposure fish were exposed to nitrite concentrations (0, 0.01, 0.1, and 1.0 mM) for 69 days. Behavioral assessments were conducted on fish chronically exposed to nitrite concentrations (0, 0.01, 0.3, and 1.0 mM) for 28 days. In both experiments gill, nose and brain was collected for biochemical and histological analysis and nitrite accumulate was significant in acute and chronic experiment. Histological analysis showed an inflammatory process and cellular alteration in acute and chronical exposure. Behavioral assessment showed a decrease in food odor preference after nitrite treatments. Results demonstrate that environmental nitrite concentrations are potentially acting as a neurotoxin that alters olfactory function. Advisors/Committee Members: Huertas, Mar (advisor), Dutton, Jessica (committee member), Garcia, Dana (committee member).

Subjects/Keywords: Olfaction; Goldfish; Fish Behavior; Nitrite; Neurotoxin; Neurotoxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Martinez, M. A. (2020). Environmental Effects Of Nitrite On Goldfish (Carassius auratus) Communication. (Masters Thesis). Texas State University – San Marcos. Retrieved from https://digital.library.txstate.edu/handle/10877/12272

Chicago Manual of Style (16^th Edition):

Martinez, Melody A. “Environmental Effects Of Nitrite On Goldfish (Carassius auratus) Communication.” 2020. Masters Thesis, Texas State University – San Marcos. Accessed January 20, 2021. https://digital.library.txstate.edu/handle/10877/12272.

MLA Handbook (7^th Edition):

Martinez, Melody A. “Environmental Effects Of Nitrite On Goldfish (Carassius auratus) Communication.” 2020. Web. 20 Jan 2021.

Vancouver:

Martinez MA. Environmental Effects Of Nitrite On Goldfish (Carassius auratus) Communication. [Internet] [Masters thesis]. Texas State University – San Marcos; 2020. [cited 2021 Jan 20]. Available from: https://digital.library.txstate.edu/handle/10877/12272.

Council of Science Editors:

Martinez MA. Environmental Effects Of Nitrite On Goldfish (Carassius auratus) Communication. [Masters Thesis]. Texas State University – San Marcos; 2020. Available from: https://digital.library.txstate.edu/handle/10877/12272

University of Texas – Austin

8. Reveron, Maria Elena, 1970-. Short and long-term effects of MDMA exposure in rodents : physiological, behavioral and neurochemical responses.

Degree: PhD, Pharmacy, 2006, University of Texas – Austin

URL: http://hdl.handle.net/2152/13072

► 3,4-methylenedioxymethamphetamine (MDMA) is a popular abused amphetamine among young adults. The possibility that MDMA intake may be neurotoxic in humans led to a wealth of… (more)

▼ 3,4-methylenedioxymethamphetamine (MDMA) is a popular abused amphetamine among young adults. The possibility that MDMA intake may be neurotoxic in humans led to a wealth of studies that demonstrated large doses of MDMA cause damage to serononin (5-HT) nerve terminals in rats and non-human primates. However, to date, the exact mechanism of MDMA-induced neurotoxicity in animals is unknown. In the first data set of this dissertation, neurochemical and thermal changes associated with experimenter-delivered repetitive doses of MDMA in mice of two different age groups were investigated. Confirming previous findings with mice, repetitive MDMA administration affected dopamine (DA) system markers. Findings revealed, significant decreases in vesicular monoamine transporter2 (VMAT2) protein and significant increases in rectal temperature in older mice compared to younger counterparts. The data suggest older mice are more sensitive to the toxic effects of MDMA and that hyperthermia might contribute to MDMA neurotoxicity. Few studies have examined MDMA effects using drug self-administration procedures. Therefore, the remaining portion of the dissertation involved a series of studies investigating behavioral and biological changes occurring as the result of shortand long-term MDMA self-administration. MDMA-stimulated lever responses, locomotor activity, thermal effects, in vivo changes in nucleus accumbens (NAcc) DA and 5-HT levels and post-mortem tissue content of DA, and 5-HT were determined after various periods of MDMA abstinence in MDMA-naïve animals, and those selfadministering over 20 daily sessions. In general, experience-dependent changes in MDMA were observed in all assessed measurements. For instance, MDMA-stimulated locomotor activation increased with experience, initial hypothermia induced by MDMA progressively reversed over time, proportional changes in NAcc DA and 5-HT were altered with experience, and depleted tissue levels of 5-HT recovered after MDMA abstinence. An additional study revealed that many of these experience-dependent changes might be mediated through actions at the 5-HT2c receptor. For instance, in animals with a single MDMA experience, the 5-HT2c antagonist SB242084 enhanced MDMA-induced NAcc DA levels and locomotor activity in a manner similar to that observed only in the long-term MDMA experienced rats. In conclusion, these results suggest MDMA intake induces physiological, neurochemical and behavioral responses that change with increased MDMA drug experience. Advisors/Committee Members: Duvauchelle, Christine L. (advisor).

Subjects/Keywords: Ecstasy (Drug); Neurotoxicology

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APA (6^th Edition):

Reveron, Maria Elena, 1. (2006). Short and long-term effects of MDMA exposure in rodents : physiological, behavioral and neurochemical responses. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/13072

Chicago Manual of Style (16^th Edition):

Reveron, Maria Elena, 1970-. “Short and long-term effects of MDMA exposure in rodents : physiological, behavioral and neurochemical responses.” 2006. Doctoral Dissertation, University of Texas – Austin. Accessed January 20, 2021. http://hdl.handle.net/2152/13072.

MLA Handbook (7^th Edition):

Reveron, Maria Elena, 1970-. “Short and long-term effects of MDMA exposure in rodents : physiological, behavioral and neurochemical responses.” 2006. Web. 20 Jan 2021.

Vancouver:

Reveron, Maria Elena 1. Short and long-term effects of MDMA exposure in rodents : physiological, behavioral and neurochemical responses. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2006. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2152/13072.

Council of Science Editors:

Reveron, Maria Elena 1. Short and long-term effects of MDMA exposure in rodents : physiological, behavioral and neurochemical responses. [Doctoral Dissertation]. University of Texas – Austin; 2006. Available from: http://hdl.handle.net/2152/13072

Michigan State University

9. Bradford, Aaron Blackwood. Involvement of the GABAa receptor in calcium-dependent toxicity of methylmercury in developing and aged cerebellum.

Degree: 2013, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:2046

► Methylmercury (MeHg) is an environmental neurotoxicant of concern because of its bioaccumulation in marine ecosystems and the susceptibility of developing cerebellum to toxicity. MeHg accumulates… (more)

▼ Methylmercury (MeHg) is an environmental neurotoxicant of concern because of its bioaccumulation in marine ecosystems and the susceptibility of developing cerebellum to toxicity. MeHg accumulates in the central nervous system with a long latency to toxicity and excretion. It induces permanent motor dysfunction through selective toxicity in cerebellar granule cells (CGCs), with developing CGCs being a particular target. Though the exact pathways by which MeHg induces neuronal death and dysfunction are not fully characterized, one of the common, central pathways by which it is hypothesized to act is through disruption of intracellular calcium concentration ([Ca2+]i). [Ca2+]i is kept low in neurons and small changes are critical for neuronal signaling. Disruption of these concentrations occurs in several cell models, characterized as an irreversible increase in [Ca2+]i over time. We sought to characterize disruption of [Ca2+]i in cerebellar slices, which retain many characteristics of whole tissue. One pathway by which methylmercury may act on intracellular calcium is through the γ-aminobutyric acid type A receptor (GABAAR), a normally inhibitory receptor that is excitatory in developing CGCs and possibly in axons and presynaptic terminals. This excitation is coupled to influx of [Ca2+]i and is critical to developmental migration of neurons and to neurotransmitter release. The interaction of GABAAR s with MeHg is partially characterized by electrophysiology and there are several experiments that suggest certain subunits of the receptors are associated with cell and developmental susceptibility. We hypothesized that both MeHg and GABAARs could have effects on [Ca2+]i in CGCs in acutely-isolated slices of cerebellum and that these effects would be dependent on age and GABAAR subunit expression. To monitor [Ca2+]i we used concentration-dependent fluorophores and imaging on confocal and epifluorescent microscopes. We first tested for [Ca2+]i changes in neonatal rat, a model frequently used previously for MeHg toxicity studies. In neonatal rat CGCs, MeHg caused a concentration-dependent increase in [Ca2+]i-dependent fluorescence within minutes. These fluorescence increases included up to about 2-fold in mature CGCs compared to starting fluorescence and up to about 3-fold increase in susceptible developing CGCs. Muscimol, a GABAAR agonist, and bicuculline, a GABAAR antagonist, are both able to reduce the effects of MeHg on [Ca2+]i. MeHg is able to increase [Ca2+]i in cerebellar slices from mice as well, and a knockout of the GABAAR α6 subunit is able to increase the susceptibility of CGCs, particularly developing CGCs, with similar 2-3 foldincreases in fluorescence. Muscimol and bicuculline reduce MeHg effects in these mice as well. Compared to developmental toxicity, aging and lifelong exposures to MeHg have not been characterized nearly as fully, and as part of a comprehensive study, the effects of MeHg and several other [Ca2+]i-dependent mechanisms were tested with these fluorescence microscopy approaches. Acute… Advisors/Committee Members: Atchison, William D, LaPres, John, Chan, Christina, Kuo, Min Hao, DeWitt, David.

Subjects/Keywords: Methylmercury; GABA – Receptors; Neurotoxicology; Biochemistry; Toxicology; Neurosciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bradford, A. B. (2013). Involvement of the GABAa receptor in calcium-dependent toxicity of methylmercury in developing and aged cerebellum. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:2046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bradford, Aaron Blackwood. “Involvement of the GABAa receptor in calcium-dependent toxicity of methylmercury in developing and aged cerebellum.” 2013. Thesis, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:2046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bradford, Aaron Blackwood. “Involvement of the GABAa receptor in calcium-dependent toxicity of methylmercury in developing and aged cerebellum.” 2013. Web. 20 Jan 2021.

Vancouver:

Bradford AB. Involvement of the GABAa receptor in calcium-dependent toxicity of methylmercury in developing and aged cerebellum. [Internet] [Thesis]. Michigan State University; 2013. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:2046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bradford AB. Involvement of the GABAa receptor in calcium-dependent toxicity of methylmercury in developing and aged cerebellum. [Thesis]. Michigan State University; 2013. Available from: http://etd.lib.msu.edu/islandora/object/etd:2046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan State University

10. Hannon, Heidi Elise. Assessing the role of the transient receptor potential A1 channel in methylmercury-induced neurotoxicity.

Degree: 2016, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:3931

►

Thesis Ph. D. Michigan State University. Comparative Medicine and Integrative Biology 2016

Methylmercury (MeHg) is an environmental contaminant which bioaccumulates in aquatic food chains and,… (more)

▼

Thesis Ph. D. Michigan State University. Comparative Medicine and Integrative Biology 2016

Methylmercury (MeHg) is an environmental contaminant which bioaccumulates in aquatic food chains and, because fish and piscivorous animal species are global commodities, the potential for human exposure to this toxicant knows no geographic boundary. Human populations exposed to MeHg, either acutely or chronically, present with severe neurologic symptoms, with the preeminent clinical sign being distal paresthesia. The definitive mechanisms by which this pathologic state arises remains elusive, though the penultimate event is widespread degeneration somatosensory neurons of the dorsal root ganglia (DRG). Moreover, following in vivo MeHg exposure, a significant reduction in the size and number of large-fiber mechanoreceptive afferents is measurable, with a relative sparing of small-fiber nociceptive afferents and motor efferents. MeHg-induced cytotoxicity has been attributed to unregulated increase in intracellular Ca2+ concentration ([Ca2+]i); this perturbation arises in kinetically distinct phases, with sources of Ca2+ including efflux from intracellular storage organelles, and influx through Ca2+-permeable ion channels. The transient receptor potential (TRP) family of ion channels has been implicated as potential targets for MeHg due to their Ca2+ permeability, high expression in DRG neurons, and polymodal means of activation. The objective of this study was to determine whether the ankyrin 1 TRP channel isoform (TRPA1) selectively confers MeHg sensitivity on large-fiber DRG, and to characterize the contribution of TRPA1 to MeHg-induced [Ca2+]i dysregulation; TRPA1 was selected as a putative target for its role as a mechanoreceptor and potential for activation via cysteine-reactive compounds. Recombinant TRPA1, when acutely exposed to MeHg in vitro, contributed to MeHg-induced [Ca2+]i dysregulation and cell death in an extracellular Ca2+ (Ca2+e)-dependent manner. MeHg-induced [Ca2+]i elevations and neurotoxicity was also Ca2+e-dependent in acute dissociations of primary DRG, however the definitive contribution of TRPA1 as a mediator of Ca2+ influx could not be confirmed. Rather, whole-cell current recordings of large-fiber DRG revealed Na+ as the primary charge carrier in agonist-induced activation of TRPA1, and the onset of [Ca2+]i disruption was dependent upon extracellular Na+. This work contributes to our understanding of the actions of MeHg on TRP channels and implicates a role for other cations in mediating MeHg-induced [Ca2+]i dysregulation.

Description based on online resource;

Advisors/Committee Members: Atchison, William D, Barman, Susan M, Flink, Michael T, Ganey, Patricia E, Yuan, Yukun.

Subjects/Keywords: TRP channels; Methylmercury; Neurotoxicology; Toxicology; Neurosciences

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APA (6^th Edition):

Hannon, H. E. (2016). Assessing the role of the transient receptor potential A1 channel in methylmercury-induced neurotoxicity. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:3931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hannon, Heidi Elise. “Assessing the role of the transient receptor potential A1 channel in methylmercury-induced neurotoxicity.” 2016. Thesis, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:3931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hannon, Heidi Elise. “Assessing the role of the transient receptor potential A1 channel in methylmercury-induced neurotoxicity.” 2016. Web. 20 Jan 2021.

Vancouver:

Hannon HE. Assessing the role of the transient receptor potential A1 channel in methylmercury-induced neurotoxicity. [Internet] [Thesis]. Michigan State University; 2016. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:3931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hannon HE. Assessing the role of the transient receptor potential A1 channel in methylmercury-induced neurotoxicity. [Thesis]. Michigan State University; 2016. Available from: http://etd.lib.msu.edu/islandora/object/etd:3931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Rochester

11. Allen, Joshua L. Persistent and sex-dependent neurotoxicity following whole-body inhalation of concentrated ambient ultrafine particles during postnatal brain development and/or adulthood in mice.

Degree: PhD, 2014, University of Rochester

URL: http://hdl.handle.net/1802/28441

► The effects of air pollutants on cardiovascular and pulmonary systems have been extensively demonstrated; accumulating evidence suggests these pollutants also target the central nervous system… (more)

▼ The effects of air pollutants on cardiovascular and pulmonary systems have been extensively demonstrated; accumulating evidence suggests these pollutants also target the central nervous system (CNS). Epidemiological studies in humans link ambient air pollutant exposure with CNS diseases and dysfunctions such as schizophrenia, autism, ADHD, and cognitive decline. Given that early postnatal brain development represents a period of rapid brain development and increased susceptibility to environmental neurotoxicants, our studies sought to determine if exposure to concentrated ambient ultrafine particles (UFP) during the first weeks of postnatal life, in young adulthood, or both, produced neurotoxicity. UFP exposure resulted in sex-dependent behavioral toxicity, including deficits in performance under the fixed-interval (FI) schedule of food reinforcement, in memory, motor activity, and learning. Early postnatal UFP exposure also induced an impulsive phenotype in male mice, assessed by a fixed-ratio waiting-for-reward schedule of operant behavior. Sex-dependent and persistent (to at least 9 mos of age) glial activation was found in the frontal cortex and corpus callosum, consistent with sustained neuroinflammation, as were elevated glutamate levels in frontal cortex and hippocampus, consistent with excitotoxicity. Further, disruption of monoamine and amino acid neurotransmitters involved in mesocorticolimbic (midbrain, striatum, hippocampus, cortex) areas that mediate these behaviors were seen that correlated with changes in behavioral performance. Notably, a time course study revealed dilation of lateral ventricles (ventriculomegaly) selectively in males when brains were examined 24 hours following postnatal UFP exposure. Ventriculomegaly has been linked to schizophrenia, autism, and poor neurodevelopmental outcome in children; this effect likewise persisted into adulthood. Additional studies examined UFP as a risk factor for the Parkinson’s disease phenotype (PDP) in male mice in the combined paraquat and maneb (PQ+MB) model. Here, postnatal UFP reduced locomotor recovery measured 24 hours following injection of PQ+MB. These studies demonstrate the ability of UFP exposure in two distinct developmental time periods to induce protracted neurotoxicity in mice that is likely related to glial activation, changes in central neurotransmitters, and lateral ventricle dilation. These studies underscore the need for additional evaluation of the role of air pollutants as contributors to neurodevelopmental and neurodegenerative diseases and disorders.

Subjects/Keywords: Neurotoxicology; Air pollution; Ultra fine particles; Behavior; Mesocorticolimbic Dysfunction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Allen, J. L. (2014). Persistent and sex-dependent neurotoxicity following whole-body inhalation of concentrated ambient ultrafine particles during postnatal brain development and/or adulthood in mice. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/28441

Chicago Manual of Style (16^th Edition):

Allen, Joshua L. “Persistent and sex-dependent neurotoxicity following whole-body inhalation of concentrated ambient ultrafine particles during postnatal brain development and/or adulthood in mice.” 2014. Doctoral Dissertation, University of Rochester. Accessed January 20, 2021. http://hdl.handle.net/1802/28441.

MLA Handbook (7^th Edition):

Allen, Joshua L. “Persistent and sex-dependent neurotoxicity following whole-body inhalation of concentrated ambient ultrafine particles during postnatal brain development and/or adulthood in mice.” 2014. Web. 20 Jan 2021.

Vancouver:

Allen JL. Persistent and sex-dependent neurotoxicity following whole-body inhalation of concentrated ambient ultrafine particles during postnatal brain development and/or adulthood in mice. [Internet] [Doctoral dissertation]. University of Rochester; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1802/28441.

Council of Science Editors:

Allen JL. Persistent and sex-dependent neurotoxicity following whole-body inhalation of concentrated ambient ultrafine particles during postnatal brain development and/or adulthood in mice. [Doctoral Dissertation]. University of Rochester; 2014. Available from: http://hdl.handle.net/1802/28441

University of North Texas

12. Gibson, Jason. Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor.

Degree: 2015, University of North Texas

URL: https://digital.library.unt.edu/ark:/67531/metadc799542/

► A recent chemical spill of 4-Methylcyclohexanemethanol (4-MCHM) in West Virginia left 300,000 people without water. Officials claimed that this compound is not lethally toxic, but… (more)

Subjects/Keywords: GABA; 4-MCHM; cytotoxicity; neurotoxicity; receptor; Solvents – Toxicology.; Neurotoxicology.; GABA – Receptors.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gibson, J. (2015). Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor. (Thesis). University of North Texas. Retrieved from https://digital.library.unt.edu/ark:/67531/metadc799542/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gibson, Jason. “Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor.” 2015. Thesis, University of North Texas. Accessed January 20, 2021. https://digital.library.unt.edu/ark:/67531/metadc799542/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gibson, Jason. “Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor.” 2015. Web. 20 Jan 2021.

Vancouver:

Gibson J. Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor. [Internet] [Thesis]. University of North Texas; 2015. [cited 2021 Jan 20]. Available from: https://digital.library.unt.edu/ark:/67531/metadc799542/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gibson J. Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor. [Thesis]. University of North Texas; 2015. Available from: https://digital.library.unt.edu/ark:/67531/metadc799542/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Texas

13. Holmes, Katelyn. Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds.

Degree: 2015, University of North Texas

URL: https://digital.library.unt.edu/ark:/67531/metadc801913/

► Mefloquine hydrochloride is an antimalarial agent that has been used for the past 40 years. Numerous reports of neurological side effects have recently led the… (more)

▼ Mefloquine hydrochloride is an antimalarial agent that has been used for the past 40 years. Numerous reports of neurological side effects have recently led the FDA to issue a strong warning regarding long-term neurological effects. This warning lead to the U.S. Army’s Special Forces and other components to discontinue its use in July of 2013. Despite reported adverse side effects, mefloquine remains in circulation and is recommended to travelers going to specific Asian countries. Mefloquine has been used as a treatment for those already infected with the malaria parasite (blood concentrations ranging from 2.1 to 23 µM), and as prophylaxis (blood concentrations averaging 3.8 µM) (Dow 2003). The purpose of this study was to quantify Mefloquine’s toxicity using spontaneously active nerve cell networks growing on microelectrode arrays in vitro and to identify compounds that alleviate or reduce toxic effects. The current literature on mefloquine toxicity is lacking electrophysiological data. These data will contribute to research on the mechanism of adverse side effects associated with mefloquine use. Sequential titration experiments were performed by adding increasing concentrations of mefloquine solution to cultured neurons. Network responses were quantified and reversibility was examined. In each network, activity decreases were normalized as a percent of reference activity yielding a mean IC50 value of 5.97 ± 0.44 (SD) µM (n=6). After total activity loss, no activity was recovered with two successive medium changes. To test for network response desensitization resulting from sequential applications over 5-6 hr periods, one-point titrations at varying concentrations were conducted with fresh networks. These experiments yielded a single concentration response curve with an IC50 value of 2.97 µM. This represents a statistically significant shift (p < 0.0001) to lower concentrations of mefloquine, demonstrating that sequential applications result in network desensitization. After mefloquine exposures, cells were evaluated for irreversible cytotoxic damage. Over a 12-hour period under 6 µM mefloquine, process beading and granulation of somal cytoplasm were observed. At 8 µM mefloquine cell stress was apparent after only 10 minutes with major glial damage and process beading at 120 minutes. In this study, quinolinic acid served as a neuroprotectant at 20 µM. There have been multiple studies on the endogenous concentrations of quinolinic acid and current literature is quite variable. Immunocompromised individuals have some of the highest blood levels of quinolinic acid (up to 20 µM). With 30 min pre-applications of quinolinic acid, the mefloquine IC50 value shifted from 5.97 ± 0.44 µM (n=6), to 9.28 ± 0.55 µM (n=3). This represents a statistically significant change to higher mefloquine concentrations and demonstrates neuroprotection. Advisors/Committee Members: Gross, Guenter W., Fuchs, Jannon Lou, 1946-, Gopal, Kamakshi V..

Subjects/Keywords: Mefloquine; toxicity; neurotoxicity; malaria; Mefloquine – Toxicology.; Antimalarials – Toxicology.; Neurotoxicology.

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APA (6^th Edition):

Holmes, K. (2015). Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds. (Thesis). University of North Texas. Retrieved from https://digital.library.unt.edu/ark:/67531/metadc801913/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Holmes, Katelyn. “Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds.” 2015. Thesis, University of North Texas. Accessed January 20, 2021. https://digital.library.unt.edu/ark:/67531/metadc801913/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Holmes, Katelyn. “Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds.” 2015. Web. 20 Jan 2021.

Vancouver:

Holmes K. Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds. [Internet] [Thesis]. University of North Texas; 2015. [cited 2021 Jan 20]. Available from: https://digital.library.unt.edu/ark:/67531/metadc801913/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Holmes K. Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds. [Thesis]. University of North Texas; 2015. Available from: https://digital.library.unt.edu/ark:/67531/metadc801913/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan State University

14. Shafer, Timothy Joseph. Effects of the neurotoxicant methylmercury on neuronal Ca² channels : effects on Ca²⁺ channels involved in transmitter release.

Degree: PhD, Department of Pharmacology and Toxicology and Institute for environmental Toxicology, 1991, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:23367

Subjects/Keywords: Methylmercury – Toxicology; Neurotoxicology; Rats

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shafer, T. J. (1991). Effects of the neurotoxicant methylmercury on neuronal Ca² channels : effects on Ca²⁺ channels involved in transmitter release. (Doctoral Dissertation). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:23367

Chicago Manual of Style (16^th Edition):

Shafer, Timothy Joseph. “Effects of the neurotoxicant methylmercury on neuronal Ca² channels : effects on Ca²⁺ channels involved in transmitter release.” 1991. Doctoral Dissertation, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:23367.

MLA Handbook (7^th Edition):

Shafer, Timothy Joseph. “Effects of the neurotoxicant methylmercury on neuronal Ca² channels : effects on Ca²⁺ channels involved in transmitter release.” 1991. Web. 20 Jan 2021.

Vancouver:

Shafer TJ. Effects of the neurotoxicant methylmercury on neuronal Ca² channels : effects on Ca²⁺ channels involved in transmitter release. [Internet] [Doctoral dissertation]. Michigan State University; 1991. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:23367.

Council of Science Editors:

Shafer TJ. Effects of the neurotoxicant methylmercury on neuronal Ca² channels : effects on Ca²⁺ channels involved in transmitter release. [Doctoral Dissertation]. Michigan State University; 1991. Available from: http://etd.lib.msu.edu/islandora/object/etd:23367

Michigan State University

15. Yuan, Yukun. Effects of methylmercury on central synaptic transmission in rat brain slices.

Degree: PhD, Department of Pharmacology and Toxicology, 1997, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:25472

Subjects/Keywords: Methylmercury – Toxicology; Neurotoxicology; Rats

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yuan, Y. (1997). Effects of methylmercury on central synaptic transmission in rat brain slices. (Doctoral Dissertation). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:25472

Chicago Manual of Style (16^th Edition):

Yuan, Yukun. “Effects of methylmercury on central synaptic transmission in rat brain slices.” 1997. Doctoral Dissertation, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:25472.

MLA Handbook (7^th Edition):

Yuan, Yukun. “Effects of methylmercury on central synaptic transmission in rat brain slices.” 1997. Web. 20 Jan 2021.

Vancouver:

Yuan Y. Effects of methylmercury on central synaptic transmission in rat brain slices. [Internet] [Doctoral dissertation]. Michigan State University; 1997. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:25472.

Council of Science Editors:

Yuan Y. Effects of methylmercury on central synaptic transmission in rat brain slices. [Doctoral Dissertation]. Michigan State University; 1997. Available from: http://etd.lib.msu.edu/islandora/object/etd:25472

University of Hong Kong

16. Qiu, Guang. Assessment of the role of corticosterone and adiponectin in the neuroprotective effect of dietary restriction.

Degree: 2008, University of Hong Kong

URL: http://hdl.handle.net/10722/50144

Subjects/Keywords: Nutrition.; Neurotoxicology.; Polypeptides.; Corticosterone.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Qiu, G. (2008). Assessment of the role of corticosterone and adiponectin in the neuroprotective effect of dietary restriction. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/50144

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Qiu, Guang. “Assessment of the role of corticosterone and adiponectin in the neuroprotective effect of dietary restriction.” 2008. Thesis, University of Hong Kong. Accessed January 20, 2021. http://hdl.handle.net/10722/50144.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Qiu, Guang. “Assessment of the role of corticosterone and adiponectin in the neuroprotective effect of dietary restriction.” 2008. Web. 20 Jan 2021.

Vancouver:

Qiu G. Assessment of the role of corticosterone and adiponectin in the neuroprotective effect of dietary restriction. [Internet] [Thesis]. University of Hong Kong; 2008. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10722/50144.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Qiu G. Assessment of the role of corticosterone and adiponectin in the neuroprotective effect of dietary restriction. [Thesis]. University of Hong Kong; 2008. Available from: http://hdl.handle.net/10722/50144

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

17. 陈幸苗. The role of peroxynitrite in neurotoxicity and neurogenesis, friend or foe?.

Degree: 2012, University of Hong Kong

URL: http://hdl.handle.net/10722/198798

► Peroxynitrite (ONOO-), produced from the reaction of superoxide anion and nitric oxide (NO), plays important roles in many physiological and pathological processes as it is… (more)

▼ Peroxynitrite (ONOO-), produced from the reaction of superoxide anion and nitric oxide (NO), plays important roles in many physiological and pathological processes as it is far more active than its precursors. However, the lack of specific and direct detection methods slow down the pace of its related research. To this end, five new peroxynitrite probes have been tested with different properties, including HKGreen-4A, 9-32, HKYellow-AM, 9-40 and MitoPN-1. Overwhelming evidence shows peroxynitrite is responsible for neurotoxicity in cerebral ischemia-reperfusion injury. Development of drugs for scavenging ONOO- becomes an important therapeutic strategy for ischemic stroke. Danshen, the dried root of salvia miltiorrhiza Bunge, is a traditional Chinese Medicine commonly used for cerebrovascular diseases. With the screening platform based on the new probe HKYellow-AM, several hydrophilic compounds from Danshen were identified to be peroxynitrite scavengers. Among them, Salvianolic acid B (SAB) possessed the highest peroxynitrite scavenging activity. Another compound, Sodium Danshensu (SDSS), the sodium salt of Danshensu, is not only a representative active compound of Danshen but also the degradation product of these hydrophilic compounds in vivo. Therefore, the potential neuroprotective effects of SAB and SDSS were studied. Both SAB and SDSS possessed strong ONOO- scavenging activity and consequently protected neuronal cell line SH-SY5Y and cortical neurons from both ONOO- and oxygen-glucose deprivation–reoxygenation induced cell death. SDSS also inhibited ONOO- formation partly by scavenging NO and superoxide. In vivo focal cerebral ischemia-reperfusion experiments revealed that both SAB and SDSS remarkably reduced protein nitration level, cell death and infarct volume in ischemia-reperfused rat brains. However, as “coin has its two sides”, whether peroxynitrite could also act as a signaling molecule has not been well known yet. The discovery of adult neurogenesis brings hope for brain repair after ischemic stroke. Recent studies indicate low concentration of peroxynitrite promotes endothelial cell growth for angiogenesis and contributes to hypoxia-induced muscle cell proliferation. To investigate the role of peroxynitrite in neurogenesis, several experiments on neural stem/progenitor cells (NSCs) were performed. The results indicated low concentrations of peroxynitrite promoted NSCs proliferation, self-renewal and neuronal differentiation. The increased peroxynitrite during hypoxia has been visualized by MitoPN-1 staining. Meanwhile, peroxynitrite decomposition catalysts (PDCs, FeTMPyP and FeTPPS) treatment reduced hypoxia-induced peroxynitrite formation, NSCs proliferation, self-renewal and neuronal differentiation. Moreover, effects of peroxynitrite on neurogenesis were partly through activating HIF-1α correlated with enhanced Wnt/β-catenin signaling pathway. In addition, the different effects of peroxynitrite on neurogenesis and neurotoxicity depended on its concentration. In summary, five new probes with…

Subjects/Keywords: Peroxynitrite; Developmental neurobiology; Neurotoxicology

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APA (6^th Edition):

陈幸苗. (2012). The role of peroxynitrite in neurotoxicity and neurogenesis, friend or foe?. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/198798

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

陈幸苗. “The role of peroxynitrite in neurotoxicity and neurogenesis, friend or foe?.” 2012. Thesis, University of Hong Kong. Accessed January 20, 2021. http://hdl.handle.net/10722/198798.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

陈幸苗. “The role of peroxynitrite in neurotoxicity and neurogenesis, friend or foe?.” 2012. Web. 20 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

陈幸苗. The role of peroxynitrite in neurotoxicity and neurogenesis, friend or foe?. [Internet] [Thesis]. University of Hong Kong; 2012. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10722/198798.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

陈幸苗. The role of peroxynitrite in neurotoxicity and neurogenesis, friend or foe?. [Thesis]. University of Hong Kong; 2012. Available from: http://hdl.handle.net/10722/198798

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

University of Cincinnati

18. Amos-Kroohs, Robyn M. Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment.

Degree: PhD, Medicine: Molecular and Developmental Biology, 2014, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642

► Manganese (Mn) is an essential metal, but a neurotoxin when in excess of bodily requirements. The neurotoxic properties of Mn were first seen in adults… (more)

▼ Manganese (Mn) is an essential metal, but a neurotoxin when in excess of bodily requirements. The neurotoxic properties of Mn were first seen in adults following occupational inhalation exposure. Mn is associated with a Parkinson’s like disorder consisting of behavioral changes, neurological deficits, and motor deficits that include dystonia and bradykinesia. In children Mn overexposure (MnOE) is associated with cognitive deficits, behavioral disinhibition, decreased IQ, and decreased performance on school-related tasks. The neurotoxic effects of MnOE in children are increased due to an underdeveloped gastrointestinal system and the developing nervous system is vulnerable to toxins.Toxins, such as MnOE, do not occur in isolation. Toxin effects are likely modified by series of environmental elements that are risk factors for decreased developmental potential in children. Two of these, iron deficiency (FeD) and developmental stress (DS), cause detrimental effects in children and modify the harmful effects of neurotoxic metal exposure. Subclinical FeD affects up to 15% of US children and exacerbates Mn toxicity due to increased Mn bioavailability. FeD is prevalent in impoverished and low socioeconomic environments and these conditions induce DS. MnOE, FeD, and DS are combined here to model a `real world’ exposure scenario. Pregnant rats and their litters were housed in cages with a wire grid floor or standard bedding from embryonic day (E)7 to postnatal day (P)28. Dams were fed a 90% FeD or standard NIH-07 diet from E15 through P28. Within each litter, different offspring were treated with 100 mg/kg Mn (100Mn) by oral gavage or vehicle (VEH) every other day from P4 to P28. All treatments ended at weaning (P28).We posited that the combination of these factors would disrupt both DA and 5HT neurotransmitters systems, creating behavioral and cognitive deficits that were exacerbated under the combination of conditions as opposed to solely MnOE. We first investigated the combination of MnOE and FeD, verifying our FeD model and examining their combined effects on several neurotransmitter systems. We then added DS, the BAR cage, and conducted a behavioral phenotype of the animals, including behavioral assays at two different ages and cognitive assays as adults. Finally, we investigated potential molecular and mechanistic endpoints in an effort to determine how MnOE, FeD, and BAR cage, as well as the combination, might affect behavior and cognition in these rats.We found that MnOE causes spatial and non-spatial learning deficits, as well as decreases in social and sucrose preference. We also found concurrent increases in DA and DOPAC, but serotonergic systems appeared to be unaffected by MnOE. Posited interactions between MnOE, FeD diet, and BAR cage were minimal and transient, but present. DS also caused cognitive and behavioral changes. These findings implicate DAergic dysfunction in behavioral and cognitive deficits heretofore not found in a rodent model. Advisors/Committee Members: Williams, Michael (Committee Chair).

Subjects/Keywords: Toxicology; Manganese; Iron Deficiency; Developmental Stress; Neurotoxicology; Cognition

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APA (6^th Edition):

Amos-Kroohs, R. M. (2014). Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642

Chicago Manual of Style (16^th Edition):

Amos-Kroohs, Robyn M. “Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment.” 2014. Doctoral Dissertation, University of Cincinnati. Accessed January 20, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642.

MLA Handbook (7^th Edition):

Amos-Kroohs, Robyn M. “Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment.” 2014. Web. 20 Jan 2021.

Vancouver:

Amos-Kroohs RM. Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment. [Internet] [Doctoral dissertation]. University of Cincinnati; 2014. [cited 2021 Jan 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642.

Council of Science Editors:

Amos-Kroohs RM. Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment. [Doctoral Dissertation]. University of Cincinnati; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642

Michigan State University

19. Tiernan, Chelsea Tate. Effects of methylmercury in the dopamine synthesizing pheochromocytoma PC12 cell line.

Degree: 2013, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:2080

►

Thesis Ph. D. Michigan State University. Neuroscience 2013.

Methylmercury (MeHg) is a potent bioaccumulative neurotoxicant that targets discrete neuronal populations, including the nigrostriatal dopamine (NSDA)… (more)

▼

Thesis Ph. D. Michigan State University. Neuroscience 2013.

Methylmercury (MeHg) is a potent bioaccumulative neurotoxicant that targets discrete neuronal populations, including the nigrostriatal dopamine (NSDA) neuronal system. Epidemiological evidence has implicated chronic exposure to MeHg as an environmental risk factor for Parkinson disease (PD), and experimental analyses using in vivo animal and in vitro cell culture models have demonstrated that acute exposure to MeHg alters DA homeostasis, including release, reuptake, and metabolism. The purpose of the studies described in this dissertation is to characterize MeHg-induced changes in DA synthesis, release, reuptake, and metabolism, and to investigate mechanisms by which MeHg exerts its neurotoxic effects in the pheochromotocytoma (PC12) cell line. MeHg causes a concentration- and time-dependent increase in DA release. Higher concentrations (5μM) are associated with an increased incidence of cell death at later time points (60-120 min). However 2μM MeHg induces DA release by 60 min without altering cell viability. Thus this concentration and time-point was selected to examine other indices of DA homeostasis. MeHg-induced DA release is abolished by inhibition of vesicular exocytosis with reserpine, but not inhibition of membrane transport with desipramine. A role for synthesis in MeHg-induced DA release was indicated by an increase in the concentration of intracellular DA and the rate of decline of intracellular DA following acute treatment with the tyrosine hydroxylase (TH) inhibitor α-methyltyrosine (AMT). MeHg stimulates DA synthesis indicated by an increase in DOPA accumulation following treatment with the DOPA decarboxylase inhibitor NSD-1015. This is supported by the observation that MeHg elevates phosphorylation of TH at serine reside 40, without altering the total amount of TH. Moreover, MeHg-induced DA release is dependent upon DA synthesis because pre-treatment with AMT abolishes MeHg-induced DA release. MeHg induces aberrant DA metabolism. Intracellular concentrations of DOPAC are decreased, while intracellular concentrations of the intermediate metabolites DOPAL and DOPET are increased. This metabolomic profile suggests that MeHg inhibits the oxidation of DOPAL to DOPAC and thus inhibits aldehyde dehydrogenase (ALDH). MeHg does not directly impair ALDH activity. Instead, inhibition may be indirect because MeHg inhibits mitochondrial respiration and ATP synthesis, and decreases availability of the ALDH cofactor nicotinamide adenine dinucleotide (NAD). To assess the roles of extracellular and intracellular calcium (Ca²⁺) in altered DA release and metabolism, undifferentiated PC12 cells were exposed to MeHg in both the absence and presence of extracellular and/or intracellular Ca²⁺. Removal of intracellular but not extracellular Ca²⁺ attenuates MeHg-induced DA release. MeHg-impaired DA metabolism is not influenced by chelation of either Ca²⁺ source. The present findings are…

Advisors/Committee Members: Lookingland, Keith, Goudreau, John, Atchison, William, Miller, Kyle, Cobbett, Peter.

Subjects/Keywords: Methylmercury – Toxicology; Dopamine – Synthesis; Pheochromocytoma; Neurotoxicology; Neurosciences; Toxicology

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APA (6^th Edition):

Tiernan, C. T. (2013). Effects of methylmercury in the dopamine synthesizing pheochromocytoma PC12 cell line. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:2080

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tiernan, Chelsea Tate. “Effects of methylmercury in the dopamine synthesizing pheochromocytoma PC12 cell line.” 2013. Thesis, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:2080.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tiernan, Chelsea Tate. “Effects of methylmercury in the dopamine synthesizing pheochromocytoma PC12 cell line.” 2013. Web. 20 Jan 2021.

Vancouver:

Tiernan CT. Effects of methylmercury in the dopamine synthesizing pheochromocytoma PC12 cell line. [Internet] [Thesis]. Michigan State University; 2013. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:2080.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tiernan CT. Effects of methylmercury in the dopamine synthesizing pheochromocytoma PC12 cell line. [Thesis]. Michigan State University; 2013. Available from: http://etd.lib.msu.edu/islandora/object/etd:2080

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan State University

20. Jaiman-Cruz, Rosa Julia. Mechanisms of methylmercury-induced astrocyte toxicity : a comparative study between cerebellar and cortical astrocytes.

Degree: 2017, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:6885

►

"Methylmercury (MeHg) can affect both the peripheral and central nervous system; however, granule cells in the cerebellum are preferential targets of MeHg neurotoxicity. The loss… (more)

▼

"Methylmercury (MeHg) can affect both the peripheral and central nervous system; however, granule cells in the cerebellum are preferential targets of MeHg neurotoxicity. The loss of granule cell after MeHg exposure is believed to be the result of unregulated elevations in intracellular calcium concentrations ([Ca2+]i) that lead to glutamate excitotoxicity. Astrocytes are the main cell type responsible for buffering the excess extracellular glutamate levels, preventing the excitotoxicity of neurons. However, MeHg can also affect astrocytes and increase their [Ca2+]i. MeHg-induced cytotoxicity in astrocytes has been studied in the forebrain cortex. However, effects on cerebellar astrocytes are less studied. Because regional differences can occur in astrocytes between the two areas, in this dissertation we compared MeHg toxicity on cerebellar and cortical astrocytes, and aimed to understand different toxicological effects of MeHg on these astrocytes, such as, the increase in extracellular glutamate levels and cytotoxicity. After an acute exposure to MeHg, there was a regional, but not a typological difference in astrocyte viability, in where cerebellar astrocytes were more susceptible to MeHg than cortical astrocytes. One difference between cortical and cerebellar astrocytes that might contribute to the cerebellar astrocytes susceptibility to MeHg was the contribution of calcium (Ca2+) to cell death. It was found that intracellular Ca2+ plays a role in MeHg-induced cortical astrocyte death. However, both intracellular and extracellular Ca2+ contribute to cerebellar astrocyte death. Another factor that contributes to the regional susceptibility of cerebellar astrocytes to MeHg was the Ca2+-dependent vesicular release of glutamate. These releases occurred in cerebellar astrocytes and not in cortical astrocytes, and were not due to the smooth endoplasmic reticulum (SER), but to the interaction of MeHg with the mitochondria, L-type and N-type voltage-gated Ca2+ channels (VGCCs). However, there were no differences in the contribution of these intracellular storages and Ca2+ channels to the reduction of viability. MeHg can also affect the excitatory amino acid transporters (EAATs), inducing an upregulation and dysfunction of these proteins. By studying the effect of MeHg on astrocytes, we found that the Ca2+-dependent vesicular release of glutamate from cerebellar astrocytes and the dysfunction of the EAATs contribute to cerebellar astrocyte susceptibility. The noticeable effects of MeHg exposure in glutamate levels observed on cerebellar astrocytes might contribute to the preferential sensitivity of the granule cells to MeHg by further increasing neuronal excitotoxicity."-Pages ii-iii.

Online resource;

Advisors/Committee Members: Atchison, William D., Sortwell, Caryl, Hegg, Colleen, Gulbransen, Brian.

Subjects/Keywords: Methylmercury – Toxicology; Methymercury – Physiological effect; Neurotoxicology; Astrocytes; Neurosciences; Environmental studies; Toxicology

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APA (6^th Edition):

Jaiman-Cruz, R. J. (2017). Mechanisms of methylmercury-induced astrocyte toxicity : a comparative study between cerebellar and cortical astrocytes. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:6885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jaiman-Cruz, Rosa Julia. “Mechanisms of methylmercury-induced astrocyte toxicity : a comparative study between cerebellar and cortical astrocytes.” 2017. Thesis, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:6885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jaiman-Cruz, Rosa Julia. “Mechanisms of methylmercury-induced astrocyte toxicity : a comparative study between cerebellar and cortical astrocytes.” 2017. Web. 20 Jan 2021.

Vancouver:

Jaiman-Cruz RJ. Mechanisms of methylmercury-induced astrocyte toxicity : a comparative study between cerebellar and cortical astrocytes. [Internet] [Thesis]. Michigan State University; 2017. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:6885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jaiman-Cruz RJ. Mechanisms of methylmercury-induced astrocyte toxicity : a comparative study between cerebellar and cortical astrocytes. [Thesis]. Michigan State University; 2017. Available from: http://etd.lib.msu.edu/islandora/object/etd:6885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. Barboni, Mirella Telles Salgueiro. Estudo eletrofisiológico e psicofísico em indivíduos intoxicados por vapor de mercúrio.

Degree: Mestrado, Neurociências e Comportamento, 2008, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/47/47135/tde-20052008-160405/ ;

► Objetivo. Avaliar o campo visual em ex-trabalhadores de fábricas de lâmpadas fluorescentes com diagnóstico de mercurialismo metálico crônico ocupacional, através de testes psicofísicos de campimetria… (more)

▼ Objetivo. Avaliar o campo visual em ex-trabalhadores de fábricas de lâmpadas fluorescentes com diagnóstico de mercurialismo metálico crônico ocupacional, através de testes psicofísicos de campimetria computadorizada e registros eletrofisiológicos da retina obtidos através do eletrorretinograma multifocal. Método. A avaliação psicofísica do campo visual foi realizada em 35 ex-trabalhadores (idade média = 44,2 ± 5,9 anos; 30 homens) no equipamento Humphrey Field Analyzer II (modelo 750i) em dois testes: acromático (standard automated perimetry) e azul-amarelo (short wavelength automated perimetry). O programa Visual Evoked Response Imaging System (VERISTM Science 5.0) permitiu o registro e análise dos sinais eletrofisiológicos da retina através do eletrorretinograma multifocal em 32 ex-trabalhadores (idade média = 44,6 ± 5,5 anos; 27 homens) dos 35 que realizaram os testes de campimetria computadorizada. Os resultados foram comparados com um grupo controle para o campo visual (n = 34; idade média = 43,3 ± 8,3 anos; 21 homens) e com outro grupo controle para o eletrorretinograma multifocal (n = 21; idade média = 43,5 ± 8,9 anos; 10 homens). Resultados. Os exames psicofísicos de campimetria computadorizada mostraram que há redução da sensibilidade visual em regiões centrais até 27? do campo visual. No exame acromático a diminuição da sensibilidade ocorreu, inclusive, na região foveal. O exame azul-amarelo confirmou a redução encontrada no exame acromático para regiões paracentrais até 27° de excentricidade. O eletrorretinograma multifocal apresentou redução nas amplitudes das respostas retinianas em regiões centrais até 25°, sem alteração no tempo implícito das respostas. As regiões paracentrais mostraram redução significativa para os valores de amplitude do primeiro componente negativo (N1) e do primeiro componente positivo (P1). Discussão. A redução na sensibilidade visual em diferentes regiões do campo visual, confirma que há prejuízos no sistema visual decorrentes da exposição crônica ao vapor de mercúrio. Nesse caso, não se pode especificar as regiões afetadas, porque a metodologia utilizada não permite isolar estruturas da via visual e, consequentemente, não permite localizar as regiões específicas que o mercúrio estaria prejudicando preferencialmente. Os prejuízos causados pela intoxicação ao vapor de mercúrio na retina parecem ser difusos, considerando que a redução de amplitude das respostas de N1 e P1 pode indicar prejuízos em diferentes grupos celulares da retina. Os resultados mostram que parte dos prejuízos de campo visual causados pelo vapor de mercúrio estão relacionados com alterações retinianas. Os resultados estão de acordo com trabalhos preliminares que monstraram alterações visuais que permanecem mesmo anos após o afastamento da fonte de exposição, sugerindo que a intoxicação por vapor de mercúrio pode não ser totalmente reversível. Conclusão. Os sujeitos expostos cronicamente ao vapor de mercúrio durante um período de 10 anos (em média) apresentam redução da sensibilidade visual em diferentes regiões… Advisors/Committee Members: Ventura, Dora Selma Fix.

Subjects/Keywords: campo visual; electrophysiology; eletrofisiologia; intoxicação por mercúrio; mercury poisining; neurotoxicologia; neurotoxicology; psicofísica; psychophysics; visual field

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APA (6^th Edition):

Barboni, M. T. S. (2008). Estudo eletrofisiológico e psicofísico em indivíduos intoxicados por vapor de mercúrio. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/47/47135/tde-20052008-160405/ ;

Chicago Manual of Style (16^th Edition):

Barboni, Mirella Telles Salgueiro. “Estudo eletrofisiológico e psicofísico em indivíduos intoxicados por vapor de mercúrio.” 2008. Masters Thesis, University of São Paulo. Accessed January 20, 2021. http://www.teses.usp.br/teses/disponiveis/47/47135/tde-20052008-160405/ ;.

MLA Handbook (7^th Edition):

Barboni, Mirella Telles Salgueiro. “Estudo eletrofisiológico e psicofísico em indivíduos intoxicados por vapor de mercúrio.” 2008. Web. 20 Jan 2021.

Vancouver:

Barboni MTS. Estudo eletrofisiológico e psicofísico em indivíduos intoxicados por vapor de mercúrio. [Internet] [Masters thesis]. University of São Paulo; 2008. [cited 2021 Jan 20]. Available from: http://www.teses.usp.br/teses/disponiveis/47/47135/tde-20052008-160405/ ;.

Council of Science Editors:

Barboni MTS. Estudo eletrofisiológico e psicofísico em indivíduos intoxicados por vapor de mercúrio. [Masters Thesis]. University of São Paulo; 2008. Available from: http://www.teses.usp.br/teses/disponiveis/47/47135/tde-20052008-160405/ ;

Vanderbilt University

22. Chakraborty, Sudipta. Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes.

Degree: PhD, Neuroscience, 2015, Vanderbilt University

URL: http://hdl.handle.net/1803/10795

► Parkinson’s disease (PD) is a neurodegenerative, motor disorder that is characterized by selective dopaminergic cell loss in the substantia nigra pars compacta. About 10-20% of… (more)

Subjects/Keywords: Parkinsons disease; manganese; neurotoxicology; C. elegans; parkin; pink1; dj1; ferroportin; DMT1; oxidative stress

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chakraborty, S. (2015). Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10795

Chicago Manual of Style (16^th Edition):

Chakraborty, Sudipta. “Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/10795.

MLA Handbook (7^th Edition):

Chakraborty, Sudipta. “Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes.” 2015. Web. 20 Jan 2021.

Vancouver:

Chakraborty S. Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/10795.

Council of Science Editors:

Chakraborty S. Gene-Environment Interactions Between Manganese Toxicity and Early-Onset Parkinson's Disease Genes. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/10795

Michigan State University

23. Colón-Rodríguez, Alexandra. Role of a alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor on methylmercury-induced calcium dysregulation on motor neurons.

Degree: 2017, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:6968

►

Methylmercury (MeHg) is a persistent environmental neurotoxicant to which humans are exposed mainly through the consumption of fish. MeHg leads to neuronal cell death in… (more)

▼

Methylmercury (MeHg) is a persistent environmental neurotoxicant to which humans are exposed mainly through the consumption of fish. MeHg leads to neuronal cell death in acute or chronic exposure and its mechanism of toxicity is not yet understood. Due to its high prevalence in the environment and its mechanism of toxicity MeHg has been considered a possible contributor to the development of Amyotrophic Lateral Sclerosis (ALS). Alterations in glutamate reuptake and Ca2+ regulation in ALS and after MeHg exposures have been well documented. Most importantly, MeHg-induced alterations in intracellular Ca2+ ([Ca2+]i) in motor neurons lead to early onset ALS-like phenotype in the superoxide dismutase 1 (SOD1-G93A) mouse, a mouse model genetically susceptible to ALS. One of the ion channels that contribute to the alterations in [Ca2+]i observed in ALS and after MeHg exposure is the ionotropic glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). My research has focused on characterizing the effects of MeHg on motor neurons in vitro. I used two cell lines: a mouse motor neuron hybrid cell line NSC34 and an induced pluripotent stem cell derived-motor neuron (hiPSC-MN) cell line of human origin. I investigated MeHg toxicity in these cell types and on AMPA receptors in order to understand the role these ion channels play in the observed alterations in [Ca2+]i. Results from the studies in this dissertation demonstrate that MeHg exposure in vivo or in vitro lead to alterations in the AMPA receptor and the RNA editing enzyme ADAR2 gene expression. Also, that hiPSC-MNs are more susceptible than NSC34 cells to MeHg toxicity observed as an earlier concentration dependent cell death. I also identified that MeHg induces a bi-phasic increase in [Ca2+]i in hiPSC-MNs and Ca2+ permeable AMPA receptors are mediating those increases. Taken together these results suggest a potential role of the AMPA receptors in MeHg-induced toxicity in MNs. These findings contribute to the understanding of MeHg-induced toxicity in motor neurons and provide a platform for ongoing studies in our lab which are focused on identifying the underlying mechanisms by which MeHg is contributing to the accelerated onset of ALS-like phenotype.

Online resource;

Advisors/Committee Members: Atchison, William D, Ganey, Patricia, Fyfe, John, Jordan, Cynthia.

Subjects/Keywords: Motor neurons; Methylmercury – Toxicology; Methylmercury – Physiological effect; Calcium – Physiological effect; Neurotoxicology; Neurosciences; Toxicology

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APA (6^th Edition):

Colón-Rodríguez, A. (2017). Role of a alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor on methylmercury-induced calcium dysregulation on motor neurons. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:6968

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Colón-Rodríguez, Alexandra. “Role of a alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor on methylmercury-induced calcium dysregulation on motor neurons.” 2017. Thesis, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:6968.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Colón-Rodríguez, Alexandra. “Role of a alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor on methylmercury-induced calcium dysregulation on motor neurons.” 2017. Web. 20 Jan 2021.

Vancouver:

Colón-Rodríguez A. Role of a alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor on methylmercury-induced calcium dysregulation on motor neurons. [Internet] [Thesis]. Michigan State University; 2017. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:6968.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Colón-Rodríguez A. Role of a alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor on methylmercury-induced calcium dysregulation on motor neurons. [Thesis]. Michigan State University; 2017. Available from: http://etd.lib.msu.edu/islandora/object/etd:6968

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan State University

24. Tew, Jason C. The nematode Caenorhabditis elegans : a model organism for study of methyl mercury toxicity.

Degree: MS, Biochemistry and Molecular Biology, 2008, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:16678

Subjects/Keywords: Caenorhabditis elegans – Research; Methylmercury – Research; Neurotoxicology

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APA (6^th Edition):

Tew, J. C. (2008). The nematode Caenorhabditis elegans : a model organism for study of methyl mercury toxicity. (Masters Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:16678

Chicago Manual of Style (16^th Edition):

Tew, Jason C. “The nematode Caenorhabditis elegans : a model organism for study of methyl mercury toxicity.” 2008. Masters Thesis, Michigan State University. Accessed January 20, 2021. http://etd.lib.msu.edu/islandora/object/etd:16678.

MLA Handbook (7^th Edition):

Tew, Jason C. “The nematode Caenorhabditis elegans : a model organism for study of methyl mercury toxicity.” 2008. Web. 20 Jan 2021.

Vancouver:

Tew JC. The nematode Caenorhabditis elegans : a model organism for study of methyl mercury toxicity. [Internet] [Masters thesis]. Michigan State University; 2008. [cited 2021 Jan 20]. Available from: http://etd.lib.msu.edu/islandora/object/etd:16678.

Council of Science Editors:

Tew JC. The nematode Caenorhabditis elegans : a model organism for study of methyl mercury toxicity. [Masters Thesis]. Michigan State University; 2008. Available from: http://etd.lib.msu.edu/islandora/object/etd:16678

University of Hong Kong

25. 陳楓. Prenatal dioxins and polychlorinated biphenyl (PCB) exposure and neurodevelopment of children : a systematic review.

Degree: 2015, University of Hong Kong

URL: http://hdl.handle.net/10722/221741

► Purpose: Dioxins and Polychlorinated biphenyls (PCBs) are neurotoxic. This systematic review reviews the literature onthe association between prenatal dioxin/PCB exposure and neurodevelopment in infants and… (more)

Subjects/Keywords: Neurotoxicology; Neurotoxic agents; Dioxins - Health aspects

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

陳楓. (2015). Prenatal dioxins and polychlorinated biphenyl (PCB) exposure and neurodevelopment of children : a systematic review. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/221741

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

陳楓. “Prenatal dioxins and polychlorinated biphenyl (PCB) exposure and neurodevelopment of children : a systematic review.” 2015. Thesis, University of Hong Kong. Accessed January 20, 2021. http://hdl.handle.net/10722/221741.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

陳楓. “Prenatal dioxins and polychlorinated biphenyl (PCB) exposure and neurodevelopment of children : a systematic review.” 2015. Web. 20 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

陳楓. Prenatal dioxins and polychlorinated biphenyl (PCB) exposure and neurodevelopment of children : a systematic review. [Internet] [Thesis]. University of Hong Kong; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10722/221741.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

陳楓. Prenatal dioxins and polychlorinated biphenyl (PCB) exposure and neurodevelopment of children : a systematic review. [Thesis]. University of Hong Kong; 2015. Available from: http://hdl.handle.net/10722/221741

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

26. Bhatia, Inderjeet. Cellular and molecular mechanisms of bilirubin induced neural cell apoptosis and respective therapeutic interventions.

Degree: 2004, University of Hong Kong

URL: http://hdl.handle.net/10722/31027

Subjects/Keywords: Bilirubin.; Apoptosis - Molecular aspects.; Neurotoxicology.; Neurons.

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APA (6^th Edition):

Bhatia, I. (2004). Cellular and molecular mechanisms of bilirubin induced neural cell apoptosis and respective therapeutic interventions. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/31027

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bhatia, Inderjeet. “Cellular and molecular mechanisms of bilirubin induced neural cell apoptosis and respective therapeutic interventions.” 2004. Thesis, University of Hong Kong. Accessed January 20, 2021. http://hdl.handle.net/10722/31027.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bhatia, Inderjeet. “Cellular and molecular mechanisms of bilirubin induced neural cell apoptosis and respective therapeutic interventions.” 2004. Web. 20 Jan 2021.

Vancouver:

Bhatia I. Cellular and molecular mechanisms of bilirubin induced neural cell apoptosis and respective therapeutic interventions. [Internet] [Thesis]. University of Hong Kong; 2004. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10722/31027.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bhatia I. Cellular and molecular mechanisms of bilirubin induced neural cell apoptosis and respective therapeutic interventions. [Thesis]. University of Hong Kong; 2004. Available from: http://hdl.handle.net/10722/31027

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

27. Saddik, Basema. Assessing neurotoxicity of working children between the ages of 10-17 in Lebanon.

Degree: Medicine. Public Health and Community Medicine, 2005, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/68626 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:69762/SOURCE01?view=true

Subjects/Keywords: Neurotoxicology; Child labor; Thesis Digitisation Program

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APA (6^th Edition):

Saddik, B. (2005). Assessing neurotoxicity of working children between the ages of 10-17 in Lebanon. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/68626 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:69762/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Saddik, Basema. “Assessing neurotoxicity of working children between the ages of 10-17 in Lebanon.” 2005. Doctoral Dissertation, University of New South Wales. Accessed January 20, 2021. http://handle.unsw.edu.au/1959.4/68626 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:69762/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Saddik, Basema. “Assessing neurotoxicity of working children between the ages of 10-17 in Lebanon.” 2005. Web. 20 Jan 2021.

Vancouver:

Saddik B. Assessing neurotoxicity of working children between the ages of 10-17 in Lebanon. [Internet] [Doctoral dissertation]. University of New South Wales; 2005. [cited 2021 Jan 20]. Available from: http://handle.unsw.edu.au/1959.4/68626 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:69762/SOURCE01?view=true.

Council of Science Editors:

Saddik B. Assessing neurotoxicity of working children between the ages of 10-17 in Lebanon. [Doctoral Dissertation]. University of New South Wales; 2005. Available from: http://handle.unsw.edu.au/1959.4/68626 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:69762/SOURCE01?view=true

University of Washington

28. Petroff, Rebekah Lee. Neurological Effects of Low-Level, Chronic Domoic Acid Exposure in a Nonhuman Primate Model.

Degree: PhD, 2020, University of Washington

URL: http://hdl.handle.net/1773/45987

► Global oceans play an important role in many aspects of human life. We build our homes on the shores, take our food from the waters,… (more)

▼ Global oceans play an important role in many aspects of human life. We build our homes on the shores, take our food from the waters, and create our economies from the wealth of resources in marine waters. There is a growing recognition, however, that certain species of marine algae produce potent toxins that can accumulate in seafood and pose health risks to human and wildlife populations. Domoic acid (DA), the focus of this dissertation, is produced by algae in the genus Pseudo-nitzschia. DA is a potent glutamate receptor agonist and neurotoxin, and high-dose exposure to this toxin has been associated with severe illness and permanent memory loss. Although there are strict regulatory limits preventing human exposures greater than 0.075-0.1 mg/kg, recent studies have suggested that repeated and chronic exposures below these levels may affect memory and learning in adults (Grattan et al., 2016, 2018). The studies described in this dissertation took place as part of a larger investigation on the reproductive and developmental consequences of low-dose, chronic DA exposure during pregnancy in a nonhuman primate model (Macaca fascicularis). Early results from this study demonstrated that daily, oral exposure to 0.075 to 0.15 mg DA/kg/day for up to two years, induced symptoms in adults that were manifested as intention tremors (Burbacher et al., 2019). Given that previous studies have found oral doses up to ten times greater than those used in the present study were not overtly toxic, this observation was unexpected (Truelove et al., 1998). The three experiments detailed in Chapters 2, 3 and 4 were designed to further identify the brain’s structural, physiological, and cellular effects in this unique cohort of animals and provide a greater understanding of the health risks associated with chronic, low-dose DA exposure. In the first study, in vivo work using magnetic resonance imaging (MRI) demonstrated that the previously observed intention tremors were associated with white matter deficits in a key neural circuit involved in memory processing, including the fornix and internal capsule (Petroff et al., 2019). In the second study, electroencephalography (EEG) data were collected from sedated adult females, and results suggested subtle changes in power of DA-exposed animals that may be associated with neurophysiological changes (Petroff, et al., submitted). The final body of work in this dissertation integrates these findings by using in vivo MRI scans and ex vivo histopathology to understand the cellular level effects of low-level chronic exposure to DA. Study data revealed that animals exposed to DA and displaying clinical symptomology have a higher incidence of focal microglia reactions, which may be related to the observed decreases in white matter integrity and due to the activation of neuroinflammation pathways (Petroff et al., in preparation). Collectively, the studies described in this dissertation provide the first data on chronic, low-dose oral exposure in a preclinical nonhuman primate model and explore the… Advisors/Committee Members: Burbacher, Thomas M (advisor).

Subjects/Keywords: domoic acid; low-level; neurotoxicology; nonhuman primate; oral exposure; Toxicology; Public health; Environmental health; Environmental health

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Petroff, R. L. (2020). Neurological Effects of Low-Level, Chronic Domoic Acid Exposure in a Nonhuman Primate Model. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/45987

Chicago Manual of Style (16^th Edition):

Petroff, Rebekah Lee. “Neurological Effects of Low-Level, Chronic Domoic Acid Exposure in a Nonhuman Primate Model.” 2020. Doctoral Dissertation, University of Washington. Accessed January 20, 2021. http://hdl.handle.net/1773/45987.

MLA Handbook (7^th Edition):

Petroff, Rebekah Lee. “Neurological Effects of Low-Level, Chronic Domoic Acid Exposure in a Nonhuman Primate Model.” 2020. Web. 20 Jan 2021.

Vancouver:

Petroff RL. Neurological Effects of Low-Level, Chronic Domoic Acid Exposure in a Nonhuman Primate Model. [Internet] [Doctoral dissertation]. University of Washington; 2020. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1773/45987.

Council of Science Editors:

Petroff RL. Neurological Effects of Low-Level, Chronic Domoic Acid Exposure in a Nonhuman Primate Model. [Doctoral Dissertation]. University of Washington; 2020. Available from: http://hdl.handle.net/1773/45987

Hong Kong University of Science and Technology

29. Yu, Chi Wang. NMDA receptor mediated toxicity in primary neuronal cultures from rodent cerebral cortex.

Degree: 2004, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-3908 ; https://doi.org/10.14711/thesis-b843341 ; http://repository.ust.hk/ir/bitstream/1783.1-3908/1/th_redirect.html

► In various neurological disorders, excess glutamate over-stimulates N-methyl-D-aspartate receptors (NMDARs) leading to excess calcium influx and subsequent neuronal injury and death. NMDAR and extracellular calcium… (more)

▼ In various neurological disorders, excess glutamate over-stimulates N-methyl-D-aspartate receptors (NMDARs) leading to excess calcium influx and subsequent neuronal injury and death. NMDAR and extracellular calcium ([Ca2+]o) have long been shown to be necessary for excitotoxicity, however, the relationship between [Ca2+]o, NMDAR activity and NMDA-induced cytotoxicity is still unclear. Here, I used cultures of primary cortical neurons as a model system to investigate the relationships. The use of a specific antagonist, ifenprodil, revealed that NMDA-induced cytotoxicity in these cultures was mainly mediated by NR2B-containing NMDARs. Both ifenprodil and APV totally blocked NMDA-induced cytotoxicity. Consistently, NMDA-induced whole cell current was ~971.3 pA, while that supplemented with ifenprodil and APV were ~125.9 pA and ~14.0 pA, respectively. Parallel patch-clamping experiments and lactate dehydrogenase (LDH) cytotoxicity assays with a wide range of NMDA concentrations revealed that NMDA-induced cytotoxicity was directly correlated to NMDA-induced whole-cell currents in these cultures. A positive linear correlation was observed by plotting NMDA-induced cytotoxicity vs. NMDA-induced whole-cell currents. Performing LDH cytotoxicity assays, complete dose/response curves of the NMDA-induced cytotoxicity were obtained at different extracellular calcium concentrations (0.27 - 27 mM) and plotted vs. NMDA-induced whole-cell currents. Fitting curves using four parameter logistic equation showed that elevated [Ca2+]o, augmented NMDA-induced cytotoxicity by shifting the curves leftwards. By obtaining Hill slopes from the curves, this potentiation of NMDA toxic effect could be explained by the fractional calcium current (Pf) at a given [Ca2+]o, as derived from the Goldman-Hodgkin-Katz (GHK) equation on the basis of constant field assumptions. The Pf of NMDAR at 2.7 mM [Ca2+]o, which is ~21.5%, was calculated using GHK equation. These results support the notion that NMDA-induced excitotoxicity is limited by its intrinsic biophysical property, Pf, but not its subsequent intracellular neurotoxic signaling pathways near the NMDARs. Activating and blocking fluxes from other sources (non-NMDAR and VSCC) failed to significantly modulate NMDA-induced cytotoxicity. This result further supports the essential role of Ca2+ influx through NMDAR in neurotoxic process. To characterize the role of synaptic NMDARs in excitotoxicity, synaptic glutamate release was stimulated by high K+ exposure. High K+ exposure was not toxic at physiological [Ca2+]o, but induced toxicity at elevated [Ca2+]o. Comparing with toxicities induced by NMDA bath applications, NMDARs stimulated by high K+ exposure was found to be equivalent to that by ~10 μM NMDA. By using these numbers as reference, I calculated that synaptic NMDARs were contributing ~14.5% of NMDA-induced whole cell current.

Subjects/Keywords: Methyl aspartate – Receptors ; Calcium – Physiological effect ; Neurotoxicology

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APA (6^th Edition):

Yu, C. W. (2004). NMDA receptor mediated toxicity in primary neuronal cultures from rodent cerebral cortex. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-3908 ; https://doi.org/10.14711/thesis-b843341 ; http://repository.ust.hk/ir/bitstream/1783.1-3908/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yu, Chi Wang. “NMDA receptor mediated toxicity in primary neuronal cultures from rodent cerebral cortex.” 2004. Thesis, Hong Kong University of Science and Technology. Accessed January 20, 2021. http://repository.ust.hk/ir/Record/1783.1-3908 ; https://doi.org/10.14711/thesis-b843341 ; http://repository.ust.hk/ir/bitstream/1783.1-3908/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yu, Chi Wang. “NMDA receptor mediated toxicity in primary neuronal cultures from rodent cerebral cortex.” 2004. Web. 20 Jan 2021.

Vancouver:

Yu CW. NMDA receptor mediated toxicity in primary neuronal cultures from rodent cerebral cortex. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2004. [cited 2021 Jan 20]. Available from: http://repository.ust.hk/ir/Record/1783.1-3908 ; https://doi.org/10.14711/thesis-b843341 ; http://repository.ust.hk/ir/bitstream/1783.1-3908/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yu CW. NMDA receptor mediated toxicity in primary neuronal cultures from rodent cerebral cortex. [Thesis]. Hong Kong University of Science and Technology; 2004. Available from: http://repository.ust.hk/ir/Record/1783.1-3908 ; https://doi.org/10.14711/thesis-b843341 ; http://repository.ust.hk/ir/bitstream/1783.1-3908/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

IUPUI

30. Brittain, Joel Matthew. Dual regulation of voltage- and ligand-gated calcium channels by collapsin response mediator protein 2.

Degree: 2013, IUPUI

URL: http://hdl.handle.net/1805/3613

►

Indiana University-Purdue University Indianapolis (IUPUI)

Synaptic transmission is coordinated by a litany of protein-protein interactions that rely on the proper localization and function of pre-… (more)

▼

Indiana University-Purdue University Indianapolis (IUPUI)

Synaptic transmission is coordinated by a litany of protein-protein interactions that rely on the proper localization and function of pre- and post-synaptic Ca2+ channels. The axonal guidance/specification collapsin response mediator protein-2 (CRMP-2) was identified as a potential partner of the pre-synaptic N-type voltage-gated Ca2+ channel (CaV2.2). CRMP-2 bound directly to CaV2.2 in two regions; the channel domain I-II intracellular loop and the distal C-terminus. Both proteins co-localized within presynaptic sites in hippocampal neurons. Overexpression in hippocampal neurons of a CRMP-2 protein fused to EGFP caused a significant increase in Ca2+ channel current density whereas lentivirus-mediated CRMP-2 knockdown abolished this effect. Cell surface biotinylation studies showed an increased number of CaV2.2 at the cell surface in CRMP-2–overexpressing neurons. Both activity- and CRMP-2-phosphoryation altered the interaction between CaV2.2 and CRMP-2. I identified a CRMP-2-derived peptide (called CBD3) that bound CaV2.2 and effectively disrupted the interaction between CaV2.2 and CRMP-2. CBD3 peptide fused to the HIV TAT protein (TAT-CBD3) decreased neuropeptide release from sensory neurons and excitatory synaptic transmission in dorsal horn neurons, and reversed neuropathic hypersensitivity produced by an antiretroviral drug. Unchecked Ca2+ influx via N-methyl-D-aspartate receptors (NMDARs) has been linked to activation of neurotoxic cascades culminating in cell death (i.e. excitotoxicity). CRMP-2 was suggested to affect NMDAR trafficking and possibly involved in neuronal survival following excitotoxicity. Based upon these studies, I hypothesized that a peptide from CRMP2 could preserve neurons in the face of excitotoxic challenges. Lentiviral–mediated CRMP2 knockdown or treatment with TAT-CBD3 blocked neuronal death following glutamate exposure likely via blunting toxicity from NMDAR-mediated delayed calcium deregulation. TAT-CBD3 induced internalization of the NMDAR subunit NR2B in dendritic spines without altering somal surface expression. TAT-CBD3 reduced NMDA-mediated Ca2+-influx and currents in cultured neurons. The presented work validates CRMP-2 as a novel modulator of pre- and post-synaptic Ca2+ channels and provides evidence that the TAT-CBD3 peptide could be useful as a potential therapeutic for both chronic neuropathic pain and excitotoxicity following stroke or other neuronal insults.

Advisors/Committee Members: Khanna, Rajesh, Cummins, Theodore R., Oxford, G. S., Quilliam, Lawrence, Thurmond, Debbie C..

Subjects/Keywords: Calcium channels, CRMP-2, NMDARs; Calcium channels – Research; Neurotransmitters; Phosphoproteins; Neuropeptides – Research; Synapses; Neurotoxicology; Neuralgia; Nervous system – Pathophysiology; Antiretroviral agents

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Brittain, J. M. (2013). Dual regulation of voltage- and ligand-gated calcium channels by collapsin response mediator protein 2. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/3613

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Brittain, Joel Matthew. “Dual regulation of voltage- and ligand-gated calcium channels by collapsin response mediator protein 2.” 2013. Thesis, IUPUI. Accessed January 20, 2021. http://hdl.handle.net/1805/3613.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Brittain, Joel Matthew. “Dual regulation of voltage- and ligand-gated calcium channels by collapsin response mediator protein 2.” 2013. Web. 20 Jan 2021.

Vancouver:

Brittain JM. Dual regulation of voltage- and ligand-gated calcium channels by collapsin response mediator protein 2. [Internet] [Thesis]. IUPUI; 2013. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1805/3613.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Brittain JM. Dual regulation of voltage- and ligand-gated calcium channels by collapsin response mediator protein 2. [Thesis]. IUPUI; 2013. Available from: http://hdl.handle.net/1805/3613

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations