subject:(endocannabinoids)

University of Aberdeen

1. Kerr, Jamie. Allosteric modulation of the CB1 receptor.

Degree: PhD, 2013, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153099890005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577607

► Bioactive compounds from Cannabis sativa have been used for millennia to alleviate the symptoms of a range of diseases. The physiological basis of effects such… (more)

▼ Bioactive compounds from Cannabis sativa have been used for millennia to alleviate the symptoms of a range of diseases. The physiological basis of effects such as analgesia, stimulation of hunger and reduction of inflammation was established in the late 20th century with the discovery of cannabinoid receptors but efforts to synthesise safe and potent drugs targeting these proteins have so far failed. The major barrier to research in this area is the instability of the receptors outside of biological settings, rendering elucidation of the binding sites by traditional means difficult. Certain small molecules can interact with the cannabinoid type 1 receptor (CB1) at locations distinct to the primary ligand docking site. Such allosteric modulation of the endocannabinoid system offers significant advantages over using orthosteric drugs and in this research a range of indole based structures were synthesised and tested in an attempt to improve the activity and drug-like nature of a lead compound. A partial structure-activity relationship was established, including the description of the most potent allosteric enhancer of CB1 so far reported. Efforts were also undertaken to investigate the allosteric binding environments using photoactivatable ligands based on a CB1 inhibitor. In combination with mutation studies and computer modelling this technique could allow the rational design of allosteric modulators, a task which is not trivial at present. Two photoactivatable compounds were synthesised and shown to interact with the receptor, with a method for isolating covalently labelled peptide fragments from other biomolecules demonstrated using “click chemistry” and a modified Wang resin. This work may find application in future investigations aiming to produce allosteric pharmaceuticals targeting CB1. Furthermore, the techniques described may be applied to study the binding site of a recently described allosteric endocannabinoid or could potentially be adapted to look at secondary binding domains in other G protein-coupled receptors.

Subjects/Keywords: 540; Cannabinoids; Endocannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Kerr, J. (2013). Allosteric modulation of the CB1 receptor. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153099890005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577607

Chicago Manual of Style (16^th Edition):

Kerr, Jamie. “Allosteric modulation of the CB1 receptor.” 2013. Doctoral Dissertation, University of Aberdeen. Accessed March 09, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153099890005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577607.

MLA Handbook (7^th Edition):

Kerr, Jamie. “Allosteric modulation of the CB1 receptor.” 2013. Web. 09 Mar 2021.

Vancouver:

Kerr J. Allosteric modulation of the CB1 receptor. [Internet] [Doctoral dissertation]. University of Aberdeen; 2013. [cited 2021 Mar 09]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153099890005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577607.

Council of Science Editors:

Kerr J. Allosteric modulation of the CB1 receptor. [Doctoral Dissertation]. University of Aberdeen; 2013. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153099890005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577607

Vanderbilt University

2. Cavener, Victoria S. Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice.

Degree: PhD, Neuroscience, 2018, Vanderbilt University

URL: http://hdl.handle.net/1803/14003

► Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice Victoria S. Cavener Dissertation under direction of Professor Sachin Patel Elucidating the underlying molecular mechanisms regulating… (more)

Subjects/Keywords: Fear extinction; DAGL; endocannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Cavener, V. S. (2018). Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14003

Chicago Manual of Style (16^th Edition):

Cavener, Victoria S. “Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice.” 2018. Doctoral Dissertation, Vanderbilt University. Accessed March 09, 2021. http://hdl.handle.net/1803/14003.

MLA Handbook (7^th Edition):

Cavener, Victoria S. “Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice.” 2018. Web. 09 Mar 2021.

Vancouver:

Cavener VS. Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice. [Internet] [Doctoral dissertation]. Vanderbilt University; 2018. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1803/14003.

Council of Science Editors:

Cavener VS. Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice. [Doctoral Dissertation]. Vanderbilt University; 2018. Available from: http://hdl.handle.net/1803/14003

University of Debrecen

3. Hakimelahi, Shapoor. The pharmaceutical role of marijuana in cancer .

Degree: DE – Általános Orvostudományi Kar, 2014, University of Debrecen

URL: http://hdl.handle.net/2437/194928

► The main focus of this thesis is finding out of whether or not marijuana (cannabis) can be used as a treatment against cancer or if… (more)

Subjects/Keywords: Cytotoxic; Cytoprotective; Endocannabinoids; biochemistry

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Hakimelahi, S. (2014). The pharmaceutical role of marijuana in cancer . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/194928

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):

Hakimelahi, Shapoor. “The pharmaceutical role of marijuana in cancer .” 2014. Thesis, University of Debrecen. Accessed March 09, 2021. http://hdl.handle.net/2437/194928.

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

MLA Handbook (7^th Edition):

Hakimelahi, Shapoor. “The pharmaceutical role of marijuana in cancer .” 2014. Web. 09 Mar 2021.

Vancouver:

Hakimelahi S. The pharmaceutical role of marijuana in cancer . [Internet] [Thesis]. University of Debrecen; 2014. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/2437/194928.

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

Council of Science Editors:

Hakimelahi S. The pharmaceutical role of marijuana in cancer . [Thesis]. University of Debrecen; 2014. Available from: http://hdl.handle.net/2437/194928

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

University of Aberdeen

4. Kerr, Jamie. Allosteric modulation of the CB1 receptor.

Degree: Dept. of Chemistry., 2013, University of Aberdeen

URL: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=196261 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=196261&custom_att_2=simple_viewer

Subjects/Keywords: Cannabinoids; Endocannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Kerr, J. (2013). Allosteric modulation of the CB1 receptor. (Doctoral Dissertation). University of Aberdeen. Retrieved from http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=196261 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=196261&custom_att_2=simple_viewer

Chicago Manual of Style (16^th Edition):

Kerr, Jamie. “Allosteric modulation of the CB1 receptor.” 2013. Doctoral Dissertation, University of Aberdeen. Accessed March 09, 2021. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=196261 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=196261&custom_att_2=simple_viewer.

MLA Handbook (7^th Edition):

Kerr, Jamie. “Allosteric modulation of the CB1 receptor.” 2013. Web. 09 Mar 2021.

Vancouver:

Kerr J. Allosteric modulation of the CB1 receptor. [Internet] [Doctoral dissertation]. University of Aberdeen; 2013. [cited 2021 Mar 09]. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=196261 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=196261&custom_att_2=simple_viewer.

Council of Science Editors:

Kerr J. Allosteric modulation of the CB1 receptor. [Doctoral Dissertation]. University of Aberdeen; 2013. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=196261 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=196261&custom_att_2=simple_viewer

Universiteit Utrecht

5. Vliet, A.C. van. Pharmacological intervention in obesity Utilizing the endocannabinoid and opioid system.

Degree: 2011, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/197446

► Introduction: Obesity and its secondary chronic diseases are a massive burden on the Western healthcare system, therefore the pharmacological industry has taken an interest in… (more)

Subjects/Keywords: Obesity; endocannabinoids; opioids; polytherapy; food intake

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Vliet, A. C. v. (2011). Pharmacological intervention in obesity Utilizing the endocannabinoid and opioid system. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/197446

Chicago Manual of Style (16^th Edition):

Vliet, A C van. “Pharmacological intervention in obesity Utilizing the endocannabinoid and opioid system.” 2011. Masters Thesis, Universiteit Utrecht. Accessed March 09, 2021. http://dspace.library.uu.nl:8080/handle/1874/197446.

MLA Handbook (7^th Edition):

Vliet, A C van. “Pharmacological intervention in obesity Utilizing the endocannabinoid and opioid system.” 2011. Web. 09 Mar 2021.

Vancouver:

Vliet ACv. Pharmacological intervention in obesity Utilizing the endocannabinoid and opioid system. [Internet] [Masters thesis]. Universiteit Utrecht; 2011. [cited 2021 Mar 09]. Available from: http://dspace.library.uu.nl:8080/handle/1874/197446.

Council of Science Editors:

Vliet ACv. Pharmacological intervention in obesity Utilizing the endocannabinoid and opioid system. [Masters Thesis]. Universiteit Utrecht; 2011. Available from: http://dspace.library.uu.nl:8080/handle/1874/197446

University of Manchester

6. Listyacahyani, Anggit. THE ROLE OF THE CUTANEOUS ENDOCANNABINOID SYSTEM IN HUMAN SKIN BARRIER FORMATION.

Degree: 2019, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322429

► The skin barrier provides protection from external threats, and defects in the skin barrier are involved in several skin diseases such as atopic dermatitis, eczema,… (more)

▼ The skin barrier provides protection from external threats, and defects in the skin barrier are involved in several skin diseases such as atopic dermatitis, eczema, and psoriasis. Growing evidence suggests that endocannabinoids (EC) have a role in the biological processes of the skin including skin barrier formation. The EC system involvement in other biological barriers such as intestinal barrier, bronchial barrier and blood brain barrier has been shown to involve regulation of the tight junction (TJ) formation; this leads to the hypothesis that the EC system may also be involved in skin barrier regulation through regulation of epidermal TJ. The aim of this study was to explore the role of EC in keratinocyte differentiation and TJ functionality, two important processes in skin barrier formation, and explore the modulation of the EC system by the anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In order to address this aim, HaCaT keratinocytes, primary normal human epidermal keratinocytes (NHEK) and human skin samples were used as models. UVR and histamine were used to disrupt the barrier. Healthy volunteers were given EPA and DHA as oral supplementation and donated UVR-treated skin. EC and related N-acyl ethanolamines (NAE) and monoacyl glycerols (MAG) were analysed by UPLC/ESI-MS/MS in cells and skin samples. Enzymes (NAPE-PLD, 12-LOX, and 15-LOX2) and Langerhans cells (LC) were analysed by IHC. TJ functionality was assessed by transepithelial electrical resistance (TEER) and FITC-dextran permeability assays. Localisation of TJ proteins was assessed by IF, and protein and gene expression by western blot and RT-qPCR, respectively. EC and NAE were detected in cells and human skin samples. N-palmitoyl ethanolamine (PEA) was effective on TJ and two different paracellular pathways were investigated: the pore pathway responsible for the passage of small ions and leak pathway responsible for the passage of large molecules. TEER and FITC-Dextran assays revealed that PEA increased TJ integrity (p=0.0419) but had no effect on permeability in NHEK. PEA appears to mediate the pore pathway, supported by increased expression of claudin-4 protein (p=0.020) and claudin-4 gene expression (p=0.0011). PEA did not affect the expression of occludin and zonula occluden-1, responsible for the leak pathway. UVR did not alter the production of EC and NAE. However, increases in PEA (p=0.035), N-oleoyl ethanolamine (OEA) (p=0.022) and N-vaccenoyl ethanolamine (VEA) (p=0.024) levels in primary NHEK were observed overtime in response to histamine; this shows that NAE are involved in histamine-induced skin barrier damage. Interestingly, PEA (p=0.0123) was also able to repair the damaging effect of histamine on TJ, as shown by increased TEER. EPA and DHA had differential effects on EC in UVR-challenged skin. DHA overall decreased EC production and NAPE-PLD expression, while EPA showed an opposite effect and increased 15-LOX2. Only DHA reduced the migration of LC… Advisors/Committee Members: O'NEILL, CATHERINE CA, KENDALL, ALEXANDRA A, Nicolaou, Anna, O'Neill, Catherine, Kendall, Alexandra.

Subjects/Keywords: Lipidomics; Endocannabinoids; Skin barrier; Skin inflammation

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Listyacahyani, A. (2019). THE ROLE OF THE CUTANEOUS ENDOCANNABINOID SYSTEM IN HUMAN SKIN BARRIER FORMATION. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322429

Chicago Manual of Style (16^th Edition):

Listyacahyani, Anggit. “THE ROLE OF THE CUTANEOUS ENDOCANNABINOID SYSTEM IN HUMAN SKIN BARRIER FORMATION.” 2019. Doctoral Dissertation, University of Manchester. Accessed March 09, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322429.

MLA Handbook (7^th Edition):

Listyacahyani, Anggit. “THE ROLE OF THE CUTANEOUS ENDOCANNABINOID SYSTEM IN HUMAN SKIN BARRIER FORMATION.” 2019. Web. 09 Mar 2021.

Vancouver:

Listyacahyani A. THE ROLE OF THE CUTANEOUS ENDOCANNABINOID SYSTEM IN HUMAN SKIN BARRIER FORMATION. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Mar 09]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322429.

Council of Science Editors:

Listyacahyani A. THE ROLE OF THE CUTANEOUS ENDOCANNABINOID SYSTEM IN HUMAN SKIN BARRIER FORMATION. [Doctoral Dissertation]. University of Manchester; 2019. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322429

Vanderbilt University

7. Holleran, Katherine Mercedes. Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids.

Degree: PhD, Neuroscience, 2016, Vanderbilt University

URL: http://hdl.handle.net/1803/10525

► Major depressive disorder (MDD) represents an enormous societal burden that will directly affect nearly one fifth of Americans within their lifetime. Despite its high prevalence… (more)

▼ Major depressive disorder (MDD) represents an enormous societal burden that will directly affect nearly one fifth of Americans within their lifetime. Despite its high prevalence and contribution to disability, current treatment strategies – primarily SSRIs – have low efficacy and take weeks to months of treatment before alleviation of symptoms occurs. Recently, the noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist ketamine was shown to induce rapid and long lasting antidepressant effects in both rodent models of depression and MDD patients. However, the mechanism underlying ketamine’s effects are not completely known. The bed nucleus of the stria terminalis (BNST) is a part of the extended amygdala and sits at the nexus of higher order processing, reward circuitry, and stress circuitry and has been implicated in depression-like behavior. We found that antagonism of the GluN2B subunit of the NMDAR, through both global pharmacology as well as genetically restricted to the BNST, resulted in reduced depression-like behavior in the Novelty-Induced Hypophagia task (NIH). We also found that ketamine was able to reduce depression-like behavior induced by forced abstinence from a six week two bottle choice ethanol (EtOH) drinking paradigm. Female singly housed mice displayed high preference for EtOH, and drinking seemed to become habit-driven over the course of the paradigm. Protracted forced abstinence was required to induce long-lasting depression-like behaviors, which were ameliorated by ketamine, but not another NMDAR antagonist memantine. Additionally, we found that amelioration of depression-like behaviors could also be achieved by augmenting the endocannabinoid (eCB) 2-AG through inhibition of its degradation enzyme monacylglycerol (MAG) lipase by JZL-184. Antidepressant-like effects of JZL-184 were completely blocked by low dose rimonabant, a cannabinoid receptor 1 (CB1) antagonist. We found that eCB levels were altered during EtOH drinking and abstinence in the basolateral amygdala. Future studies will aim to examine the mechanisms underlying antidepressant effects eCBs and ketamine within the BNST both basally and following EtOH administration. Advisors/Committee Members: Louis Muglia (committee member), Gregg Stanwood (committee member), Danny Winder (committee member), Sachin Patel (Committee Chair).

Subjects/Keywords: Endocannabinoids; BNST; NMDA receptors; Ketamine; Depression

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Holleran, K. M. (2016). Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10525

Chicago Manual of Style (16^th Edition):

Holleran, Katherine Mercedes. “Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed March 09, 2021. http://hdl.handle.net/1803/10525.

MLA Handbook (7^th Edition):

Holleran, Katherine Mercedes. “Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids.” 2016. Web. 09 Mar 2021.

Vancouver:

Holleran KM. Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1803/10525.

Council of Science Editors:

Holleran KM. Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/10525

Vanderbilt University

8. Hermanson, Daniel John. Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects.

Degree: PhD, Chemistry, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/11000

► Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects. Daniel John Hermanson Dissertation under the direction of Professor Lawrence J. Marnett Cyclooxygenase-2… (more)

▼ Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects. Daniel John Hermanson Dissertation under the direction of Professor Lawrence J. Marnett Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) to form prostaglandins (PGs), but also inactivates endocannabinoids (eCBs) in vitro. We have identified and characterized a series of novel probes termed “substrate-selective” COX-2 inhibitors (SSCIs) that selectively inhibit eCB oxygenation with no impact on PG production. Using X-ray crystallography and site-directed mutagenesis we have elucidated the binding determinants of a series of SSCIs. The phenomenon of substrate-selective COX-2 inhibition arises from the fact that although COX-2 is a structural homodimer, it is a functional heterodimer. Kinetic analyses have revealed that substrate-selective COX-2 inhibitors bind in the allosteric COX-2 subunit and act as non-competitive inhibitors of eCB oxygenation in the catalytic subunit through a conformational change involving Leu-531. We have explored the biological impact of SSCIs in multiple settings including stimulated dorsal root ganglion cells and the brain. These studies established that SSCIs act in a COX-2-dependent manner to decrease the production of eCB-derived PGs and increase the levels of eCBs while having no impact on PG production or AA levels. Importantly, the biochemical effects of SSCIs are unique relative to other modes of COX inhibition. Augmenting eCBs in the brain with SSCIs leads to cannabinoid receptor 1 activation and anxiolytic effects in multiple pre-clinical models of anxiety. Thus, COX-2 is a critical regulator of eCB signaling in vivo. We have identified AA as a non-competitive inhibitor of eCB oxygenation by COX-2 in vitro. Inhibition of AA production in simulated macrophages through pharmacological or genetic inhibition of cytosolic phospholipase A2 (cPLA2) leads to a robust decrease in AA and PGs with increased eCB-derived PGs. Lipidomic analyses identified that this is due to enrichment of AA-containing phosphatidylinositols, diacylglycerols, and 2-arachidonoyl glycerol upon pharmacological or genetic inhibition of cPLA2. These studies classify the determinants of the oxygenation of AA and eCBs by COX-2 in stimulated macrophages. Advisors/Committee Members: H. Alex Brown (committee member), Sachin Patel (committee member), Bruce D. Carter (committee member), Ned A. Porter (committee member), Lawrence J. Marnett (Committee Chair).

Subjects/Keywords: pain; anxiety; cyclooxygenase-2; endocannabinoids; inflammation; NSAIDs

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Hermanson, D. J. (2014). Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11000

Chicago Manual of Style (16^th Edition):

Hermanson, Daniel John. “Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed March 09, 2021. http://hdl.handle.net/1803/11000.

MLA Handbook (7^th Edition):

Hermanson, Daniel John. “Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects.” 2014. Web. 09 Mar 2021.

Vancouver:

Hermanson DJ. Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1803/11000.

Council of Science Editors:

Hermanson DJ. Substrate-selective Inhibition of Cyclooxygenase-2: Molecular Determinants, Probe Development, and In Vivo Effects. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/11000

Boston College

9. Worley, Nicholas B. Prefrontal Circuit Selection in Stress and Resilience.

Degree: PhD, Psychology, 2019, Boston College

URL: http://dlib.bc.edu/islandora/object/bc-ir:108656

► Stress is a risk factor for neuropsychiatric disorders such as post-traumatic stress disorder and depression, yet not all individuals who are exposed to stress develop… (more)

▼ Stress is a risk factor for neuropsychiatric disorders such as post-traumatic stress disorder and depression, yet not all individuals who are exposed to stress develop such disorders. Several factors influence susceptibility versus resilience to the effects of stress, including coping strategy biological sex. A growing body of research in humans has demonstrated that active coping strategies – defined as using available resources to problem solve – are positively correlated with resilience. In rodents, resilience to a potent acute stressor can be achieved through active coping, such as controlling the termination of a stressor, but only in males. During controllable stress males engage a stress mitigating pathway between the prelimbic (PL) and dorsal raphe nucleus (DRN), but this pathway isn’t engaged by control in females or when stress is uncontrollable in both sexes. Thus, neural activity within the ventromedial prefrontal cortex (vmPFC) is a critical determinant of stressor-induced anxiety. The mechanism that engage vmPFC excitability are not well understood. Therefore, the goals of the dissertation were 1) determine if eCBs in the PL promote neuronal excitability and behavioral resilience 2) test if ES and IS result in differential activation PL afferents, and will specifically test if ES results in greater activation PL-inputs from action-outcome associated regions, while IS leads to greater engagement of stress/fear inputs to the PL, and 3) identify network-wide patterns of activation and test the hypothesis that the stress and action-outcome networks are differentially activated as a function of stressor controllability and/or sex. We’ve demonstrated that augmenting eCBs in the PL increased excitability through a CB1 and GABA receptor dependent mechanism and was sufficient to block the stress induced decrease in social exploration. Regarding goal 2, PL inputs from the orbitofrontal cortex and DRN were activated in response to stress per se, but were not sensitive to stressor controllability and did not differ between males and females. PL afferents from the basolateral amygdala and mediodorsally thalamus were not sensitive to stress. Lastly, we quantified Fos expression in response to controllable and uncontrollable stress in male and female rats in 24 brain regions associated with stress, action-outcome learning, and showing sex differences in response to stress. Using interregional correlations, we found differences in functional connectivity as a function of stressor controllability and sex when considering all 24 regions and when considering only stress associated regions. Females showed greater overall functional connectivity compared with males, and IS resulted in greater overall connectivity than ES. We also reveal potentially important nodes in functional connectivity networks using centrality measures to identify network hubs. The findings of this research emphasize the need to study differences between males and females across all realms of neuroscience, particularly in relation to disorders of… Advisors/Committee Members: John P. Christianson (Thesis advisor).

Subjects/Keywords: endocannabinoids; prefrontal cortex; resilience; sex differences; stress

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Worley, N. B. (2019). Prefrontal Circuit Selection in Stress and Resilience. (Doctoral Dissertation). Boston College. Retrieved from http://dlib.bc.edu/islandora/object/bc-ir:108656

Chicago Manual of Style (16^th Edition):

Worley, Nicholas B. “Prefrontal Circuit Selection in Stress and Resilience.” 2019. Doctoral Dissertation, Boston College. Accessed March 09, 2021. http://dlib.bc.edu/islandora/object/bc-ir:108656.

MLA Handbook (7^th Edition):

Worley, Nicholas B. “Prefrontal Circuit Selection in Stress and Resilience.” 2019. Web. 09 Mar 2021.

Vancouver:

Worley NB. Prefrontal Circuit Selection in Stress and Resilience. [Internet] [Doctoral dissertation]. Boston College; 2019. [cited 2021 Mar 09]. Available from: http://dlib.bc.edu/islandora/object/bc-ir:108656.

Council of Science Editors:

Worley NB. Prefrontal Circuit Selection in Stress and Resilience. [Doctoral Dissertation]. Boston College; 2019. Available from: http://dlib.bc.edu/islandora/object/bc-ir:108656

University of Adelaide

10. Christie, Stewart David. Endocannabinoid regulation of gastric vagal afferent signalling.

Degree: 2020, University of Adelaide

URL: http://hdl.handle.net/2440/126014

► Background: Gastric vagal afferents (GVAs) play a role in peripheral appetite control. Tension sensitive GVAs respond to stretch or distension of the stomach sending signals… (more)

▼ Background: Gastric vagal afferents (GVAs) play a role in peripheral appetite control. Tension sensitive GVAs respond to stretch or distension of the stomach sending signals to the hindbrain to produce feelings of fullness and satiety. The sensitivity of tension sensitive GVAs is reduced in diet-induced obesity which may contribute to increased meal size. Further, transient receptor potential vanilloid 1 (TRPV1) knockout mice also show decreased GVA tension receptor sensitivity. Endocannabinoids (ECs) regulate appetite via cannabinoid 1 (CB1) receptors and are also endogenous ligands for TRPV1. The CB1 receptor and TRPV1 are expressed on GVAs and the CB1 receptor is also expressed on gastric ghrelin cells. Further, the endocannabinoid anandamide (AEA; ligand for CB1) is expressed in the stomach. However, it is not known if ECs, ghrelin, and TRPV1 interact to regulate GVA sensitivity. Aims: To determine in lean and diet induced obese mice: 1. The co-expression of CB1, TRPV1, and ghrelin receptor (growth hormone secretagogue receptor; GHSR) in individual GVA cell bodies. 2. The effect of AEA on GVA sensitivity and secondary messenger pathways involved. 3. The effect of AEA and ghrelin on the expression of orexigenic receptors in nodose ganglia. Methods: Retrograde tracing was used to identify single GVA cell bodies in the nodose ganglia which was then combined with single cell QRT-PCR. An in vitro electrophysiology preparation was used to determine the effects of methanandamide (mAEA; stable analogue of AEA) on the sensitivity of GVAs in C57BL/6 mice fed ad libitum with either a standard laboratory diet (SLD) or high fat diet (HFD). This was performed with mAEA alone or in combination with antagonists to determine possible secondary messenger pathways. Nodose ganglia were cultured for 14 hours in a medium containing mAEA or ghrelin and then analysed via QRT-PCR for changes in receptor or ion channel expression. Results: CB1, TRPV1, and GHSR were expressed and co-expressed in individual tension sensitive GVA neurons in a diet-dependent manner. In SLD-mice mAEA exhibited concentration-dependent dual inhibitory and excitatory effects on the mechanosensitivity of tension sensitive GVAs. This was abolished to a single inhibitory effect regardless of concentration in HFD-mice. In cultured vagal afferent cell bodies, exposure to mAEA and ghrelin altered the expression of CB1, TRPV1, and GHSR mRNA in a diet dependent manner. Conclusions: ECs, acting through CB1 and TRPV1, have a pivotal role in modulating GVA satiety signals depending on the second messenger pathway utilised. In HFD-mice only an inhibitory effect is observed. These changes may contribute to the development and/or maintenance of obesity. Advisors/Committee Members: Page, Amanda (advisor), Li, Hui (advisor), Adelaide Medical School (school).

Subjects/Keywords: Endocannabinoids; gastric vagal afferents; TRPV1; ghrelin

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Christie, S. D. (2020). Endocannabinoid regulation of gastric vagal afferent signalling. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/126014

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):

Christie, Stewart David. “Endocannabinoid regulation of gastric vagal afferent signalling.” 2020. Thesis, University of Adelaide. Accessed March 09, 2021. http://hdl.handle.net/2440/126014.

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

MLA Handbook (7^th Edition):

Christie, Stewart David. “Endocannabinoid regulation of gastric vagal afferent signalling.” 2020. Web. 09 Mar 2021.

Vancouver:

Christie SD. Endocannabinoid regulation of gastric vagal afferent signalling. [Internet] [Thesis]. University of Adelaide; 2020. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/2440/126014.

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

Council of Science Editors:

Christie SD. Endocannabinoid regulation of gastric vagal afferent signalling. [Thesis]. University of Adelaide; 2020. Available from: http://hdl.handle.net/2440/126014

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

University of Toronto

11. Lin, Lin. The regulation of tissue n-acylethanolamine and arachidonoylglycerol concentrations by diet, ischemia, n-acyl phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase.

Degree: PhD, 2018, University of Toronto

URL: http://hdl.handle.net/1807/89882

► Dietary fatty acids (DFAs) can modulate levels of n-acylethanolamines (NAEs) and arachidonoylglycerols (AGs) via the synthetic enzyme, n-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and degradation enzyme, fatty… (more)

▼ Dietary fatty acids (DFAs) can modulate levels of n-acylethanolamines (NAEs) and arachidonoylglycerols (AGs) via the synthetic enzyme, n-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and degradation enzyme, fatty acid amide hydrolase (FAAH). However, other parallel pathways maybe also involved. This research hypothesizes that the absence of NAPE-PLD will lower tissue NAEs; while the absence of FAAH will increase NAEs. Also, basal NAE and AG levels are lower than ischemia-induced levels, while DFA can modulate basal NAE levels. In study 1, wild-type (C57BL/6), NAPE-PLD (-/+) and NAPE-PLD (-/-) mice were fed AIN-93G diets enriched with beef tallow, canola oil, corn oil or fish oil for nine weeks then killed by microwave fixation. Results showed that NAPE-PLD (-/-) had lower levels of plasma and jejunum oleoylethanolamide (OEA), lower food intake, body weight, and body fat composition than wild-type. Also, corn oil diet elevated arachidonoylethanolamide (AEA) and AGs; while fish oil elevated docosahexaenoylethanolamide (DHEA) in all genotypes. Therefore, NAPE-PLD is specific to OEA, but not other NAE, which may play a role in regulating body composition and weight management. Also, DFA can still elevate NAE levels without NAPE-PLD suggesting it is not necessary for dietary increased NAEs. In study 2, wild-type and FAAH-KO mice were fed a standard chow diet for 9 weeks; then killed by control (microwave fixation) or partial CO2-induced ischemia or CO2-induced ischemia. Brain NAE levels were higher in the FAAH-KO than the wild-type. Interestingly, CO2-induced ischemia increased all NAEs and AGs in the wild-type mice, but only DHEA was increased in the FAAH-KO mice. Thus, FAAH may play an essential role in regulating lipid metabolism in response to ischemia. In conclusion, this work provides evidence that diet, NAPE-PLD, FAAH and ischemia are independently involved in maintaining tissue NAE levels. Advisors/Committee Members: Bazinet, Richard P, Nutritional Sciences.

Subjects/Keywords: diets; endocannabinoids; fatty acids; metabolism; mice; 0570

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Lin, L. (2018). The regulation of tissue n-acylethanolamine and arachidonoylglycerol concentrations by diet, ischemia, n-acyl phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89882

Chicago Manual of Style (16^th Edition):

Lin, Lin. “The regulation of tissue n-acylethanolamine and arachidonoylglycerol concentrations by diet, ischemia, n-acyl phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase.” 2018. Doctoral Dissertation, University of Toronto. Accessed March 09, 2021. http://hdl.handle.net/1807/89882.

MLA Handbook (7^th Edition):

Lin, Lin. “The regulation of tissue n-acylethanolamine and arachidonoylglycerol concentrations by diet, ischemia, n-acyl phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase.” 2018. Web. 09 Mar 2021.

Vancouver:

Lin L. The regulation of tissue n-acylethanolamine and arachidonoylglycerol concentrations by diet, ischemia, n-acyl phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1807/89882.

Council of Science Editors:

Lin L. The regulation of tissue n-acylethanolamine and arachidonoylglycerol concentrations by diet, ischemia, n-acyl phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/89882

University of Illinois – Urbana-Champaign

12. Roy, Jahnabi. Omics approach towards understanding the function of bioactive lipids in osteosarcoma.

Degree: PhD, Chemistry, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/99506

► Osteosarcoma is the most common form of primary bone cancer in humans and well as dogs. The treatment options for OS include a multi-agent induction… (more)

▼ Osteosarcoma is the most common form of primary bone cancer in humans and well as dogs. The treatment options for OS include a multi-agent induction chemotherapy and radical excision of the tumor followed by adjuvant chemotherapy. Despite the aggressive treatment course, the survival rates are poor. In patients with localized disease, 5-year survival rates are approximately 65%. However, for metastatic disease at diagnosis or recurrence, the 5-year survival rates have plateaued to only 20%. Although progress has been made towards improving treatment options, the early detection and subsequent control of metastasis have been challenging in OS. This work is aimed at discovering the various proteomic and lipidomic biomarkers in metastatic and non-metastatic osteosarcoma as well as development of lipid mediators as potential therapeutics. We take a high-throughput approach towards identifying specific membrane proteins and lipids that are differentially expressed in normal osteoblasts, non-metastatic and metastatic osteosarcoma. As described in chapter 2, a high throughput peptide fingerprinting enabled us to identify various membrane proteins that are differentially expressed in metastatic versus non-metastatic osteosarcoma. Membrane proteins are the largest class of drug targets and this study identifies proteins that can targets for drugs without having to overcome the delivery of drugs across the plasma membrane. However, the functional study of membrane proteins is complicated by the fact that they exist in an amphipathic environment and lose their structure in aqueous buffers. Thus we stabilize the membrane proteome of osteosarcoma cells in nanodiscs (chapter 3). Nanodiscs are lipid bilayers surrounded by membrane scaffold protein and provide the amphipathic environment for membrane proteins. In this study we showed that lipid composition affects the protein composition incorporated. Since lipid composition affects protein incorporation and lipid-protein interactions are important for cell signaling processes, we investigated the global cellular lipidome of osteosarcoma and osteoblast cells through a high throughput lipidomics approach (chapter 4). We identified that several lipid classes and lipid species are differentially regulated in normal cells versus non-metastatic cells vs metastatic cells. These include both structural lipids as well as signaling lipids. Since signaling lipids play an important role in various physiological functions, we chose to further explore the role of a specific class of signaling lipids, known as endocannabinoid epoxides, in osteosarcoma (chapter 5). Endocannabinoid epoxides are metabolites of omega-3 fatty acids that arise from a cross-talk of phospholipase D and cytochrome P450 epoxygenase enzymes. They have previously been shown to have anti-inflammatory and anti-angiogenic properties. In this study, we show that they also possess anti-tumorigenic activity. Furthermore, we synthesize novel analogs of specific endocannabinoid epoxides that show reduced susceptibility to… Advisors/Committee Members: Das, Aditi (advisor), van der Donk, Wilfred A (Committee Chair), Fan, Timothy M (committee member), Chan, Jefferson (committee member).

Subjects/Keywords: Osteosarcoma; Omics; Lipids; Endocannabinoids; Mass spectrometry

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Roy, J. (2017). Omics approach towards understanding the function of bioactive lipids in osteosarcoma. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/99506

Chicago Manual of Style (16^th Edition):

Roy, Jahnabi. “Omics approach towards understanding the function of bioactive lipids in osteosarcoma.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed March 09, 2021. http://hdl.handle.net/2142/99506.

MLA Handbook (7^th Edition):

Roy, Jahnabi. “Omics approach towards understanding the function of bioactive lipids in osteosarcoma.” 2017. Web. 09 Mar 2021.

Vancouver:

Roy J. Omics approach towards understanding the function of bioactive lipids in osteosarcoma. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/2142/99506.

Council of Science Editors:

Roy J. Omics approach towards understanding the function of bioactive lipids in osteosarcoma. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/99506

University of Aberdeen

13. Ford, Lorna. An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells.

Degree: School of Medical Sciences., 2009, University of Aberdeen

URL: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=33596 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=33596&custom_att_2=simple_viewer

Subjects/Keywords: Bones.; Osteoclasts.; Endocannabinoids.

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Ford, L. (2009). An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells. (Doctoral Dissertation). University of Aberdeen. Retrieved from http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=33596 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=33596&custom_att_2=simple_viewer

Chicago Manual of Style (16^th Edition):

Ford, Lorna. “An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells.” 2009. Doctoral Dissertation, University of Aberdeen. Accessed March 09, 2021. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=33596 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=33596&custom_att_2=simple_viewer.

MLA Handbook (7^th Edition):

Ford, Lorna. “An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells.” 2009. Web. 09 Mar 2021.

Vancouver:

Ford L. An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells. [Internet] [Doctoral dissertation]. University of Aberdeen; 2009. [cited 2021 Mar 09]. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=33596 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=33596&custom_att_2=simple_viewer.

Council of Science Editors:

Ford L. An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells. [Doctoral Dissertation]. University of Aberdeen; 2009. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=33596 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=33596&custom_att_2=simple_viewer

Northeastern University

14. Liu, Yingpeng. Novel Endocannabinoids And Cannabilactones.

Degree: 2019, Northeastern University

URL: http://hdl.handle.net/2047/D20356167

► N-arachidonoylethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG) are the two well recognized endocannabinoids (eCBs) for the CB receptors, which are currently being targeted for a number… (more)

▼ N-arachidonoylethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG) are the two well recognized endocannabinoids (eCBs) for the CB receptors, which are currently being targeted for a number of conditions including pain, inflammation, CNS disorders and cancer. However, the metabolic instability of the eCBs hampers studies aimed at understanding the biological role(s) of these lipids. Meanwhile, structural modifications to enhance the biological activities and target specificities of the labile eCB lipids while increasing their metabolic stability, is a challenge. Here we present the development of novel AEA and 2-AG analogues with high binding affinities for CB receptors, agonist properties, and increased stabilities to the actions of hydrolytic and/or oxidative enzymes. My approach includes: a) incorporate chiral centers and steric hindrance at strategic positions; b) explore the head group of 2-AG with special emphasis on the ester moiety and the methylene linker; c) add tail constraints to AEA the n-pentyl tail region. The novel analogs demonstrates metabolic stability while maintaining similar or enhanced bioactivities which will serve as very useful probes for in vivo studies of the eCB system. In addition, my Ph.D research also includes synthesizing novel, side chain functionalized cannabinergic cannabilactone analogues in a short-cut synthetic approach, which greatly improved the overall yields with even lesser steps, compared with our earlier reported method. This efficient protocol was compatible with multiple functional groups as well, providing quick access to pharmacophore exploration of cannabilactones. The new approach expedited the synthesis of analogs and derivatives of the cannabilactone template with structural modifications at the four potential pharmacophoric regions. A series of novel functionalized cannabilactones were synthesized and their bio-activities were evaluated in vitro against the cannabinoid receptors CB1 and CB2. Some cannabilactones showed promising cannabinergic effects, which were expected to have great potential in anti-inflammation treatments and pain control.

Subjects/Keywords: cannabilactones; endocannabinoids; Chemistry; Biochemistry; Organic chemistry

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Liu, Y. (2019). Novel Endocannabinoids And Cannabilactones. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20356167

Chicago Manual of Style (16^th Edition):

Liu, Yingpeng. “Novel Endocannabinoids And Cannabilactones.” 2019. Doctoral Dissertation, Northeastern University. Accessed March 09, 2021. http://hdl.handle.net/2047/D20356167.

MLA Handbook (7^th Edition):

Liu, Yingpeng. “Novel Endocannabinoids And Cannabilactones.” 2019. Web. 09 Mar 2021.

Vancouver:

Liu Y. Novel Endocannabinoids And Cannabilactones. [Internet] [Doctoral dissertation]. Northeastern University; 2019. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/2047/D20356167.

Council of Science Editors:

Liu Y. Novel Endocannabinoids And Cannabilactones. [Doctoral Dissertation]. Northeastern University; 2019. Available from: http://hdl.handle.net/2047/D20356167

University of Manchester

15. Sunarwidhi, Anggit. The role of the cutaneous endocannabinoid system in human skin barrier formation.

Degree: PhD, 2019, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-the-cutaneous-endocannabinoid-system-in-human-skin-barrier-formation(04875d09-313f-4360-8fbe-a3826844a55b).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799329

► The skin barrier provides protection from external threats, and defects in the skin barrier are involved in several skin diseases such as atopic dermatitis, eczema,… (more)

▼ The skin barrier provides protection from external threats, and defects in the skin barrier are involved in several skin diseases such as atopic dermatitis, eczema, and psoriasis. Growing evidence suggests that endocannabinoids (EC) have a role in the biological processes of the skin including skin barrier formation. The EC system involvement in other biological barriers such as intestinal barrier, bronchial barrier and blood brain barrier has been shown to involve regulation of the tight junction (TJ) formation; this leads to the hypothesis that the EC system may also be involved in skin barrier regulation through regulation of epidermal TJ. The aim of this study was to explore the role of EC in keratinocyte differentiation and TJ functionality, two important processes in skin barrier formation, and explore the modulation of the EC system by the anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In order to address this aim, HaCaT keratinocytes, primary normal human epidermal keratinocytes (NHEK) and human skin samples were used as models. UVR and histamine were used to disrupt the barrier. Healthy volunteers were given EPA and DHA as oral supplementation and donated UVR-treated skin. EC and related N-acyl ethanolamines (NAE) and monoacyl glycerols (MAG) were analysed by UPLC/ESI-MS/MS in cells and skin samples. Enzymes (NAPE-PLD, 12-LOX, and 15-LOX2) and Langerhans cells (LC) were analysed by IHC. TJ functionality was assessed by transepithelial electrical resistance (TEER) and FITC-dextran permeability assays. Localisation of TJ proteins was assessed by IF, and protein and gene expression by western blot and RT-qPCR, respectively. EC and NAE were detected in cells and human skin samples. N-palmitoyl ethanolamine (PEA) was effective on TJ and two different paracellular pathways were investigated: the pore pathway responsible for the passage of small ions and leak pathway responsible for the passage of large molecules. TEER and FITC-Dextran assays revealed that PEA increased TJ integrity (p=0.0419) but had no effect on permeability in NHEK. PEA appears to mediate the pore pathway, supported by increased expression of claudin-4 protein (p=0.020) and claudin-4 gene expression (p=0.0011). PEA did not affect the expression of occludin and zonula occluden-1, responsible for the leak pathway. UVR did not alter the production of EC and NAE. However, increases in PEA (p=0.035), N-oleoyl ethanolamine (OEA) (p=0.022) and N-vaccenoyl ethanolamine (VEA) (p=0.024) levels in primary NHEK were observed overtime in response to histamine; this shows that NAE are involved in histamine-induced skin barrier damage. Interestingly, PEA (p=0.0123) was also able to repair the damaging effect of histamine on TJ, as shown by increased TEER. EPA and DHA had differential effects on EC in UVR-challenged skin. DHA overall decreased EC production and NAPE-PLD expression, while EPA showed an opposite effect and increased 15-LOX2. Only DHA reduced the migration of LC…

Subjects/Keywords: Skin barrier; Skin inflammation; Lipidomics; Endocannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Sunarwidhi, A. (2019). The role of the cutaneous endocannabinoid system in human skin barrier formation. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-the-cutaneous-endocannabinoid-system-in-human-skin-barrier-formation(04875d09-313f-4360-8fbe-a3826844a55b).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799329

Chicago Manual of Style (16^th Edition):

Sunarwidhi, Anggit. “The role of the cutaneous endocannabinoid system in human skin barrier formation.” 2019. Doctoral Dissertation, University of Manchester. Accessed March 09, 2021. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-the-cutaneous-endocannabinoid-system-in-human-skin-barrier-formation(04875d09-313f-4360-8fbe-a3826844a55b).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799329.

MLA Handbook (7^th Edition):

Sunarwidhi, Anggit. “The role of the cutaneous endocannabinoid system in human skin barrier formation.” 2019. Web. 09 Mar 2021.

Vancouver:

Sunarwidhi A. The role of the cutaneous endocannabinoid system in human skin barrier formation. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Mar 09]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-the-cutaneous-endocannabinoid-system-in-human-skin-barrier-formation(04875d09-313f-4360-8fbe-a3826844a55b).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799329.

Council of Science Editors:

Sunarwidhi A. The role of the cutaneous endocannabinoid system in human skin barrier formation. [Doctoral Dissertation]. University of Manchester; 2019. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-the-cutaneous-endocannabinoid-system-in-human-skin-barrier-formation(04875d09-313f-4360-8fbe-a3826844a55b).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799329

Dalhousie University

16. Slusar, Joanna. Examination of the Neuroprotective Effects of URB597 in Young and Aged Rat Retina.

Degree: MS, Department of Pharmacology with Neuroscience, 2010, Dalhousie University

URL: http://hdl.handle.net/10222/13126

► Anandamide (AEA), a well characterized endocannabinoid that has actions at multiple targets in the eye, may have potential as a novel therapeutic in the treatment… (more)

Subjects/Keywords: aging; endocannabinoids; retinal vasculature; optic nerve injury; neuroprotection; ischemia

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Slusar, J. (2010). Examination of the Neuroprotective Effects of URB597 in Young and Aged Rat Retina. (Masters Thesis). Dalhousie University. Retrieved from http://hdl.handle.net/10222/13126

Chicago Manual of Style (16^th Edition):

Slusar, Joanna. “Examination of the Neuroprotective Effects of URB597 in Young and Aged Rat Retina.” 2010. Masters Thesis, Dalhousie University. Accessed March 09, 2021. http://hdl.handle.net/10222/13126.

MLA Handbook (7^th Edition):

Slusar, Joanna. “Examination of the Neuroprotective Effects of URB597 in Young and Aged Rat Retina.” 2010. Web. 09 Mar 2021.

Vancouver:

Slusar J. Examination of the Neuroprotective Effects of URB597 in Young and Aged Rat Retina. [Internet] [Masters thesis]. Dalhousie University; 2010. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/10222/13126.

Council of Science Editors:

Slusar J. Examination of the Neuroprotective Effects of URB597 in Young and Aged Rat Retina. [Masters Thesis]. Dalhousie University; 2010. Available from: http://hdl.handle.net/10222/13126

Vanderbilt University

17. Mitchener, Michelle Marie. A. Competition and allostery govern substrate selectivity of cyclooxygenase-2 B. Enzymatic oxidation of M1dG in the genome.

Degree: PhD, Chemistry, 2017, Vanderbilt University

URL: http://hdl.handle.net/1803/15119

► Part A: Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and its ester analog, 2-arachidonoylglycerol (2-AG), to prostaglandins (PGs) and prostaglandin glyceryl esters (PG-Gs), respectively. Although the… (more)

▼ Part A: Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and its ester analog, 2-arachidonoylglycerol (2-AG), to prostaglandins (PGs) and prostaglandin glyceryl esters (PG-Gs), respectively. Although the efficiency of oxygenation of these substrates by COX-2 in vitro is similar, cellular biosynthesis of PGs far exceeds that of PG-Gs. Evidence that the homodimeric COX enzymes are functional heterodimers comprising a catalytic and an allosteric subunit suggests that competitive interaction of AA and 2-AG at the allosteric site of COX-2 might result in differential regulation of the oxygenation of the two substrates when both are present. Modulation of AA levels in RAW264.7 macrophages uncovered an inverse correlation between cellular AA levels and PG-G biosynthesis. In vitro kinetic analysis using purified protein demonstrated that the inhibition of 2-AG oxygenation by high concentrations of AA far exceeded the inhibition of AA oxygenation by high concentrations of 2-AG. An unbiased systems-based mechanistic model of the kinetic data revealed that binding of AA or 2-AG at the allosteric site of COX-2 results in a decreased catalytic efficiency of the enzyme toward 2-AG, whereas 2-AG binding at the allosteric site increases COX-2's efficiency toward AA. The results suggest that substrates interact with COX-2 via multiple potential complexes involving binding to both the catalytic and allosteric sites. Competition between AA and 2-AG for these sites, combined with differential allosteric modulation, gives rise to a complex interplay between the substrates, leading to preferential oxygenation of AA. Part B: Lipid and DNA peroxidation give rise to DNA adducts, the most abundant of which is 3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG). Increased levels of M1dG are positively correlated with a variety of physiological and pathophysiological conditions including aging, bacterial infection, and cancer. Recently, our laboratory reported the oxidative metabolism of M1dG to 6-oxo-M1dG in nuclear DNA isolated from multiple human and rodent cell lines. Heat-denaturation or proteinase K-treatment of nuclear lysates ablated conversion of M1dG to 6-oxo-M1dG in double-stranded oligonucleotides, suggesting that the oxidation is enzymatic. Preincubation of nuclear lysates with iron or alpha-ketoglutarate increased 6-oxo-M1dG formation, and nuclear lysates preincubated with either N-oxalylglycine or IOX1, two structurally distinct broad-spectrum alpha-ketoglutarate-dependent dioxygenase inhibitors, showed reduced 6-oxo-M1dG formation. Finally, treatment of RKO cells with JIB-04, a pan alpha-ketoglutarate-dependent Jumonji histone demethylase inhibitor, resulted in reduced levels of genomic 6-oxo-M1dG along with a concomitant increase in levels of M1dG. Collectively, these findings indicate the presence of a nuclear enzyme capable of converting M1dG to 6-oxo-M1dG in genomic DNA and support the hypothesis that the enzyme is a member of the alpha-ketoglutarate-dependent dioxygenase class of… Advisors/Committee Members: Ned A. Porter (committee member), Walter J. Chazin (committee member), Brian O. Bachmann (committee member), Lawrence J. Marnett (Committee Chair).

Subjects/Keywords: M1dG; chemical kinetics; endocannabinoids; cyclooxygenase-2; DNA adducts

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Mitchener, M. M. (2017). A. Competition and allostery govern substrate selectivity of cyclooxygenase-2 B. Enzymatic oxidation of M1dG in the genome. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15119

Chicago Manual of Style (16^th Edition):

Mitchener, Michelle Marie. “A. Competition and allostery govern substrate selectivity of cyclooxygenase-2 B. Enzymatic oxidation of M1dG in the genome.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed March 09, 2021. http://hdl.handle.net/1803/15119.

MLA Handbook (7^th Edition):

Mitchener, Michelle Marie. “A. Competition and allostery govern substrate selectivity of cyclooxygenase-2 B. Enzymatic oxidation of M1dG in the genome.” 2017. Web. 09 Mar 2021.

Vancouver:

Mitchener MM. A. Competition and allostery govern substrate selectivity of cyclooxygenase-2 B. Enzymatic oxidation of M1dG in the genome. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1803/15119.

Council of Science Editors:

Mitchener MM. A. Competition and allostery govern substrate selectivity of cyclooxygenase-2 B. Enzymatic oxidation of M1dG in the genome. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/15119

Washington State University

18. [No author]. CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation .

Degree: 2019, Washington State University

URL: http://hdl.handle.net/2376/17863

► Environmentally induced cocaine relapse is a major impediment in the treatment of substance use disorders. Re-exposure to a cocaine-associated context can trigger the retrieval of… (more)

Subjects/Keywords: Neurosciences; Biology; Psychobiology; amygdala; CB1; cocaine; endocannabinoids; memory; reconsolidation

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

author], [. (2019). CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation . (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/17863

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):

author], [No. “CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation .” 2019. Thesis, Washington State University. Accessed March 09, 2021. http://hdl.handle.net/2376/17863.

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

MLA Handbook (7^th Edition):

author], [No. “CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation .” 2019. Web. 09 Mar 2021.

Vancouver:

author] [. CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation . [Internet] [Thesis]. Washington State University; 2019. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/2376/17863.

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

Council of Science Editors:

author] [. CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation . [Thesis]. Washington State University; 2019. Available from: http://hdl.handle.net/2376/17863

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

University of Manitoba

19. Siemens, Linda. The effects of endocannabinoids and fatty acids on lipid metabolism and mitochondrial function in adipocytes.

Degree: Human Nutritional Sciences, 2016, University of Manitoba

URL: http://hdl.handle.net/1993/31203

► The endocannabinoid (EC) system has a role in metabolic homeostasis. The purpose of this study was to determine the effect of ECs and the fatty… (more)

Subjects/Keywords: Endocannabinoids; Fatty acids; Lipolysis; Insulin signaling; Mitochondrial function; Adipocytes

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Siemens, L. (2016). The effects of endocannabinoids and fatty acids on lipid metabolism and mitochondrial function in adipocytes. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/31203

Chicago Manual of Style (16^th Edition):

Siemens, Linda. “The effects of endocannabinoids and fatty acids on lipid metabolism and mitochondrial function in adipocytes.” 2016. Masters Thesis, University of Manitoba. Accessed March 09, 2021. http://hdl.handle.net/1993/31203.

MLA Handbook (7^th Edition):

Siemens, Linda. “The effects of endocannabinoids and fatty acids on lipid metabolism and mitochondrial function in adipocytes.” 2016. Web. 09 Mar 2021.

Vancouver:

Siemens L. The effects of endocannabinoids and fatty acids on lipid metabolism and mitochondrial function in adipocytes. [Internet] [Masters thesis]. University of Manitoba; 2016. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1993/31203.

Council of Science Editors:

Siemens L. The effects of endocannabinoids and fatty acids on lipid metabolism and mitochondrial function in adipocytes. [Masters Thesis]. University of Manitoba; 2016. Available from: http://hdl.handle.net/1993/31203

University of Ottawa

20. Kinden, Renee. Cannabinoids & Stress: The Impact of Endogenous and Exogenous Cannabinoids on Anxiety Behaviors In an Acute Stress Model .

Degree: 2015, University of Ottawa

URL: http://hdl.handle.net/10393/32784

► Although the impact of cannabinoids (CBs) on anxiety has been thoroughly studied, current research paradigms fail to incorporate acute stressors. The present study investigated the… (more)

Subjects/Keywords: Anxiety; Cannabinoids; Endocannabinoids; Exocannabinoids; HU-210; KML29; Acute Stress

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Kinden, R. (2015). Cannabinoids & Stress: The Impact of Endogenous and Exogenous Cannabinoids on Anxiety Behaviors In an Acute Stress Model . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/32784

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):

Kinden, Renee. “Cannabinoids & Stress: The Impact of Endogenous and Exogenous Cannabinoids on Anxiety Behaviors In an Acute Stress Model .” 2015. Thesis, University of Ottawa. Accessed March 09, 2021. http://hdl.handle.net/10393/32784.

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

MLA Handbook (7^th Edition):

Kinden, Renee. “Cannabinoids & Stress: The Impact of Endogenous and Exogenous Cannabinoids on Anxiety Behaviors In an Acute Stress Model .” 2015. Web. 09 Mar 2021.

Vancouver:

Kinden R. Cannabinoids & Stress: The Impact of Endogenous and Exogenous Cannabinoids on Anxiety Behaviors In an Acute Stress Model . [Internet] [Thesis]. University of Ottawa; 2015. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/10393/32784.

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

Council of Science Editors:

Kinden R. Cannabinoids & Stress: The Impact of Endogenous and Exogenous Cannabinoids on Anxiety Behaviors In an Acute Stress Model . [Thesis]. University of Ottawa; 2015. Available from: http://hdl.handle.net/10393/32784

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

University of Debrecen

21. Ben, Aurele. the endocannabinoid system and its therapeutic applications .

Degree: DE – Általános Orvostudományi Kar, University of Debrecen

URL: http://hdl.handle.net/2437/259291

► The ECS has been found to play a major role in numerous systems of the human body. It influences the central and peripheral nervous system,… (more)

Subjects/Keywords: endocannabinoids; marijuana; CB1; CB2

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Ben, A. (n.d.). the endocannabinoid system and its therapeutic applications . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/259291

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ben, Aurele. “the endocannabinoid system and its therapeutic applications .” Thesis, University of Debrecen. Accessed March 09, 2021. http://hdl.handle.net/2437/259291.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ben, Aurele. “the endocannabinoid system and its therapeutic applications .” Web. 09 Mar 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Ben A. the endocannabinoid system and its therapeutic applications . [Internet] [Thesis]. University of Debrecen; [cited 2021 Mar 09]. Available from: http://hdl.handle.net/2437/259291.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Ben A. the endocannabinoid system and its therapeutic applications . [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/259291

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of California – San Francisco

22. Larimore, Jill Suzanne. Investigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease Pathogenesis.

Degree: Neuroscience, 2012, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/80h383fv

► AbstractInvestigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease PathogenesisBy Jill LarimoreHuntington's disease (HD) is a devastating neurodegenerative disease for… (more)

▼ AbstractInvestigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease PathogenesisBy Jill LarimoreHuntington's disease (HD) is a devastating neurodegenerative disease for which there is no cure. Classically, HD is thought to result from central nervous system (CNS) dysfunction because its hallmark pathology is neurodegeneration of brain regions important for controlling movement. However, co-occurring pathologies, including severe weight loss and peripheral immune system activation, might contribute to HD progression. Given that the mutant Huntingtin protein (mHtt) is ubiquitously expressed and directly affects cells outside the CNS, an integrated understanding of mHtt-induced pathogenesis is needed. In this dissertation, I sought to understand how both central nervous and peripheral physiological systems contribute to HD pathogenesis by taking advantage of the endocannabinoid system, in which the two main cannabinoid receptors, CB1 and CB2, have distinct roles. In chapter 2, I investigated the role of CB1, which is primarily expressed in the CNS and whose expression is one of the earliest genetic changes to occur in HD-vulnerable neurons, on HD progression. We found that early genetic deletion of CB1 receptors in R6/2 mice accelerated the onset of symptoms and further decreased lifespan compared to CB1-receptor-expressing R6/2 mice, suggesting CB1 plays a functional role in HD progression. In chapter 2.1, I investigated the effects of animal weight on HD progression in BACHD mice, an overweight HD model. Specifically, using ANCOVA as a robust statistical tool, I found that changes in weight induced by deletion of CB1 expression significantly influenced HD behavior. In chapter 3, we investigated the peripheral immune system, showing that genetic deletion of CB2 in a slow-progressing HD mouse model accelerated the onset and increased the severity of motor deficits. Treatment of mice with a CB2-receptor agonist extended lifespan and suppressed motor deficits, synapse loss, and CNS inflammation, while a peripherally restricted CB2-receptor antagonist blocked these effects. CB2 regulates blood interleukin-6 levels, and interleukin-6-neutralizing antibodies partially rescued motor deficits and weight loss in HD mice. These findings support a causal link between CB2-receptor signaling in peripheral immune cells and the onset and severity of HD-induced neurodegeneration. Together, these results demonstrate that mHtt can significantly impact peripheral physiological systems, and identify novel therapeutic approaches for treating HD.

Subjects/Keywords: Neurosciences; Cannabinoid Receptor Type 2; Endocannabinoids; Huntington's disease; Peripheral Immune System

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Larimore, J. S. (2012). Investigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease Pathogenesis. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/80h383fv

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):

Larimore, Jill Suzanne. “Investigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease Pathogenesis.” 2012. Thesis, University of California – San Francisco. Accessed March 09, 2021. http://www.escholarship.org/uc/item/80h383fv.

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

MLA Handbook (7^th Edition):

Larimore, Jill Suzanne. “Investigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease Pathogenesis.” 2012. Web. 09 Mar 2021.

Vancouver:

Larimore JS. Investigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease Pathogenesis. [Internet] [Thesis]. University of California – San Francisco; 2012. [cited 2021 Mar 09]. Available from: http://www.escholarship.org/uc/item/80h383fv.

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

Council of Science Editors:

Larimore JS. Investigating the Role of Physiological Systems Outside the Central Nervous System on Huntington's Disease Pathogenesis. [Thesis]. University of California – San Francisco; 2012. Available from: http://www.escholarship.org/uc/item/80h383fv

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

University of Aberdeen

23. Goonawardena, Anushka V. Cannabinoid effects on hippocampal neurophysiology and mnemonic processing.

Degree: School of Medical Sciences., 2008, University of Aberdeen

URL: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26047 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=26047&custom_att_2=simple_viewer

Subjects/Keywords: Cannabinoids.; Receptors, Cannabinoid.; Endocannabinoids.

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Goonawardena, A. V. (2008). Cannabinoid effects on hippocampal neurophysiology and mnemonic processing. (Doctoral Dissertation). University of Aberdeen. Retrieved from http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26047 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=26047&custom_att_2=simple_viewer

Chicago Manual of Style (16^th Edition):

Goonawardena, Anushka V. “Cannabinoid effects on hippocampal neurophysiology and mnemonic processing.” 2008. Doctoral Dissertation, University of Aberdeen. Accessed March 09, 2021. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26047 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=26047&custom_att_2=simple_viewer.

MLA Handbook (7^th Edition):

Goonawardena, Anushka V. “Cannabinoid effects on hippocampal neurophysiology and mnemonic processing.” 2008. Web. 09 Mar 2021.

Vancouver:

Goonawardena AV. Cannabinoid effects on hippocampal neurophysiology and mnemonic processing. [Internet] [Doctoral dissertation]. University of Aberdeen; 2008. [cited 2021 Mar 09]. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26047 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=26047&custom_att_2=simple_viewer.

Council of Science Editors:

Goonawardena AV. Cannabinoid effects on hippocampal neurophysiology and mnemonic processing. [Doctoral Dissertation]. University of Aberdeen; 2008. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26047 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=26047&custom_att_2=simple_viewer

University of Georgia

24. Feistritzer, Rebecca Carter. The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/26313

► Stress-induced analgesia (SIA) occurs when naturally occurring brain constituents inhibit pain pathways upon exposure to a stressor and provide pain relief. These pathways involve cannabinoid… (more)

Subjects/Keywords: Endocannabinoids; CB1; CB2; Stress-Induced Analgesia; Formalin; AM251; SR144528; DGLα; LacZ

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Feistritzer, R. C. (2014). The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26313

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):

Feistritzer, Rebecca Carter. “The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior.” 2014. Thesis, University of Georgia. Accessed March 09, 2021. http://hdl.handle.net/10724/26313.

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

MLA Handbook (7^th Edition):

Feistritzer, Rebecca Carter. “The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior.” 2014. Web. 09 Mar 2021.

Vancouver:

Feistritzer RC. The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/10724/26313.

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

Council of Science Editors:

Feistritzer RC. The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26313

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

Vanderbilt University

25. Sun, Xiaofei. Studying the role of endocannabinoid signaling in reproduction.

Degree: PhD, Pharmacology, 2010, Vanderbilt University

URL: http://hdl.handle.net/1803/13018

► Marijuana is the most commonly used illicit drug, and its major active component, Δ9-tetrahydrocannabinol (Δ9-THC) exert its functions by targeting cannabinoid receptors, CNR1 and CNR2.… (more)

▼ Marijuana is the most commonly used illicit drug, and its major active component, Δ9-tetrahydrocannabinol (Δ9-THC) exert its functions by targeting cannabinoid receptors, CNR1 and CNR2. There receptors are also targeted by endocannabinoids, including anandamide. In this dissertation, we show that genetic loss of Faah, which encodes fatty acid amide hydrolase (FAAH), results in elevated levels of anandamide, an endocannabinoid, in the male reproductive system, leading to compromised fertilizing capacity of sperm. This defect is rescued by superimposing deletion of cannabinoid receptor 1 (Cnr1). Retention of Faah-/- sperm on the egg zona-pellucida provides evidence that sperm’s capacity to penetrate the zona barrier is dampened by elevated anandamide levels. Collectively, the results show that aberrant endocannabinoid signaling via CNR1 impairs normal sperm function. Besides unveiling a new regulatory mechanism of sperm function, this study has clinical significance in male fertility. Exposure to marijuana during pregnancy has adverse effects on placentation. Using mice as a model, we found that the endocannabinoid system is also present on the ectoplacental cone and spongiotrophoblast cells in placentas. We also observed that aberrant endocannabinoid signaling confers premature trophoblast stem cell differentiation, and defective trophoblast development and invasion. These defects are reflected in retarded fetal development and elevated spontaneous pregnancy loss. Because the endocannabinoid system is conserved across species, including humans, our study suggests that endocannabinoid signaling is critical to placentation and pregnancy success in humans. Collectively, my work demonstrated that appropriate endocannabinoid signaling is critical for both male and female reproductive functions. Advisors/Committee Members: Sudhansu K. Dey (committee member), Sanjoy K. Das (committee member), Lawrence J. Marnett (committee member), David L. Hachey (committee member), Richard M. Breyer (Committee Chair).

Subjects/Keywords: Placentation; Uterus; Endocannabinoids; Testis; Reproduction

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Sun, X. (2010). Studying the role of endocannabinoid signaling in reproduction. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/13018

Chicago Manual of Style (16^th Edition):

Sun, Xiaofei. “Studying the role of endocannabinoid signaling in reproduction.” 2010. Doctoral Dissertation, Vanderbilt University. Accessed March 09, 2021. http://hdl.handle.net/1803/13018.

MLA Handbook (7^th Edition):

Sun, Xiaofei. “Studying the role of endocannabinoid signaling in reproduction.” 2010. Web. 09 Mar 2021.

Vancouver:

Sun X. Studying the role of endocannabinoid signaling in reproduction. [Internet] [Doctoral dissertation]. Vanderbilt University; 2010. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1803/13018.

Council of Science Editors:

Sun X. Studying the role of endocannabinoid signaling in reproduction. [Doctoral Dissertation]. Vanderbilt University; 2010. Available from: http://hdl.handle.net/1803/13018

Vanderbilt University

26. Manna, Joseph Dominick. Identification and Characterization of a Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells.

Degree: PhD, Chemical and Physical Biology, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/12789

► Prostaglandin glycerol esters (PG-Gs) are produced by the oxygenation of the endocannabinoid, 2-arachidonoylglycerol, by cyclooxygenase 2. Understanding the role that PG-Gs play in a biological… (more)

▼ Prostaglandin glycerol esters (PG-Gs) are produced by the oxygenation of the endocannabinoid, 2-arachidonoylglycerol, by cyclooxygenase 2. Understanding the role that PG-Gs play in a biological setting has been difficult because of the hydrolytic instability of the compounds. The main focus of this research was to identify the serine hydrolase responsible for PG-Gs hydrolysis and develop tools to assess the role this enzyme has in living systems. Initially we sought to develop a new analytical method for the analysis and quantification of lipid metabolites. The most widely used methods employ chromatographic separation followed by mass spectrometric analysis, which requires significant time for sample preparation and sequential chromatography. We developed a novel high-throughput, separation-free methodology based on MALDI mass spectrometry that allows for the parallel analysis of targeted analytes. Proof-of-concept was demonstrated by analysis of prostaglandins and PG-Gs. Derivatization to incorporate a charged moiety into ketone-containing prostaglandins dramatically increased the signal-to-noise ratio relative to underivatized samples. This resulted in an increased dynamic range (15 fmol – 2000 fmol on plate) and improved linearity (r2= 0.99). The method was further adapted for high-throughput screening methods for enzymology and drug discovery. Preliminary efforts to identify the hydrolase responsible for PG-G hydrolysis utilized protein purification techniques to try and isolate the enzyme. Upon purification, three enzymes were identified, 6-phosphoglucolactonase (PGLS), platelet activating factor acetyl hydrolase 1β3 (PAFAH1β3), and dimethylarginine dimethylaminohydrolase 2 (DDAH2). Protein expression in HEK293 and siRNA knockdown in MDA-MB-231 for each identified serine hydrolase made no significant contribution to PG-G hydrolysis. The inability to isolate a specific PG-G hydrolase by protein purification caused us to take a different approach to identify the hydrolase. By comparing PG-G hydrolysis across human cancer cell types to serine hydrolase activities determined by activity-based protein profiling, we identified lysophospholipase A2 (LYPLA2) as a major enzyme responsible for PG-G hydrolysis. The principal role played by LYPLA2 in PGE2-G hydrolysis was confirmed by siRNA knockdown across multiple cancer cell types and expression in both HEK293 and E.coli. Additionally, LYPLA1, a homologue of LYPLA2, was shown to have no PGE2-G hydrolytic activity as determined by siRNA and overexpression. Purified, recombinant LYPLA2 hydrolyzed PG-Gs with the following order of activity - PGE2-G > PGF2α-G > PGD2-G but, interestingly, did not hydrolyze the endocannabinoids, 2-AG or AEA. Chemical inhibition of LYPLA2 in RAW264.7 murine macrophages-like cell lines and 1483 human head and neck squamous cell carcinoma cells elicited an increase in PG-G production. Our data indicate that LYPLA2 serves as a major PG-G hydrolase in mammalian cells. Perturbation of this enzyme should enable selective… Advisors/Committee Members: Lawrence Marnett (committee member), Alan Brash (committee member), Richard Caprioli (committee member), Ned Porter (committee member), H. Alex Brown (Committee Chair).

Subjects/Keywords: Prostaglandin Glycerol Esters; Serine hydrolases; Lysophospholipase; Endocannabinoids; Activity Based Protein Profiling

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Manna, J. D. (2014). Identification and Characterization of a Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12789

Chicago Manual of Style (16^th Edition):

Manna, Joseph Dominick. “Identification and Characterization of a Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed March 09, 2021. http://hdl.handle.net/1803/12789.

MLA Handbook (7^th Edition):

Manna, Joseph Dominick. “Identification and Characterization of a Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells.” 2014. Web. 09 Mar 2021.

Vancouver:

Manna JD. Identification and Characterization of a Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Mar 09]. Available from: http://hdl.handle.net/1803/12789.

Council of Science Editors:

Manna JD. Identification and Characterization of a Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/12789

The Ohio State University

27. Ravi, Janani. CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER.

Degree: PhD, Molecular, Cellular and Developmental Biology, 2015, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1426697196

► (i) The endocannabinoid anandamide (AEA), a neurotransmitter was shown to have anti-cancer effects. Fatty acid amide hydrolase (FAAH) metabolizes AEA and decreases its anti-tumorigenic activity.… (more)

▼ (i) The endocannabinoid anandamide (AEA), a neurotransmitter was shown to have anti-cancer effects. Fatty acid amide hydrolase (FAAH) metabolizes AEA and decreases its anti-tumorigenic activity. In this study, we have analyzed the role of FAAH inhibition in non-small cell lung cancer (NSCLC). We have shown that FAAH and CB1 receptor which is activated by AEA are expressed in lung adenocarcinoma patient samples and NSCLC cell lines A549 and H460. Since the synthetic analogue of anandamide (Met-F-AEA) did not possess significant anti-tumorigenic effects, we used Met-F-AEA in combination with FAAH inhibitor URB597 which significantly reduced EGF (epidermal growth factor)-induced proliferative and chemotactic activities in vitro when compared to anti-tumorigenic activity of Met-F-AEA alone. Further analysis of signaling mechanisms revealed that Met-F-AEA in combination with URB597 inhibits activation of EGFR and its downstream signaling ERK, AKT and NF-kB. In addition, it inhibited MMP2 secretion and stress fiber formation. We have also shown that the Met-F-AEA in combination with URB597 induces G0/G1 cell cycle arrest by downregulating cyclin D1 and CDK4 expressions, ultimately leading to apoptosis via activation of caspase-9 and PARP. Furthermore, the combination treatment inhibited tumor growth in a xenograft nude mouse model system. Tumors derived from Met-F-AEA and URB597 combination treated mice showed reduced EGFR, AKT and ERK activation and MMP2/MMP9 expressions when compared to Met-F-AEA or URB597 alone. Taken together, these data suggest in EGFR overexpressing NSCLC that the combination of Met-F-AEA with FAAH inhibitor resulted in superior therapeutic response compared to individual compound activity alone. (ii) JWH-015, a cannabinoid receptor 2 (CB2) agonist has tumor regressive property in various cancer types. However, the underlying mechanism by which it acts in lung cancer is still unknown. Tumor associated macrophage (TAM) intensity has positive correlation with tumor progression. Also, macrophages recruited at the tumor site promote tumor growth by enhancing epithelial to mesenchymal (EMT) progression. In this study, we analyzed the role of JWH-015 on EMT and macrophage infiltration by regulation of EGFR signaling. JWH-015 inhibited EMT in NSCLC cells A549 and also reversed the mesenchymal nature of CALU-1 cells by downregulation of EGFR signaling targets like ERK and STAT3. Also, in vitro co-culture experiments of A549 with M2 polarized macrophages provided evidence that JWH-015 decreased migratory and invasive abilities which was proved by reduced expression of FAK, VCAM1 and MMP2. Furthermore, it decreased macrophage induced EMT in A549 by attenuating the mesenchymal character by downregulating EGFR and its targets. These results were confirmed in an in vivo subcutaneous syngenic mouse model where JWH-015 blocks tumor growth and also inhibits macrophage recruitment and EMT at the tumor site which was regulated by EGFR pathway. Finally, JWH-015 reduced metastatic lesions in a tail vein syngenic mouse… Advisors/Committee Members: Ganju, Ramesh (Advisor).

Subjects/Keywords: Molecular Biology; Cellular Biology; Oncology; Lung cancer; endocannabinoids; synthetic cannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Ravi, J. (2015). CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1426697196

Chicago Manual of Style (16^th Edition):

Ravi, Janani. “CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER.” 2015. Doctoral Dissertation, The Ohio State University. Accessed March 09, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1426697196.

MLA Handbook (7^th Edition):

Ravi, Janani. “CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER.” 2015. Web. 09 Mar 2021.

Vancouver:

Ravi J. CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER. [Internet] [Doctoral dissertation]. The Ohio State University; 2015. [cited 2021 Mar 09]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1426697196.

Council of Science Editors:

Ravi J. CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER. [Doctoral Dissertation]. The Ohio State University; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1426697196

University of Aberdeen

28. Ford, Lorna. An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells.

Degree: PhD, 2009, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153044000005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510550

► The effects of endocannabinoids on human, mouse and rabbit bone cells were investigated. At high concentrations anandamide and 2-arachidonyl glycerol (2-AG) inhibited human osteoclast formation… (more)

Subjects/Keywords: 615.1; Bones; Osteoclasts; Endocannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Ford, L. (2009). An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153044000005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510550

Chicago Manual of Style (16^th Edition):

Ford, Lorna. “An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells.” 2009. Doctoral Dissertation, University of Aberdeen. Accessed March 09, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153044000005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510550.

MLA Handbook (7^th Edition):

Ford, Lorna. “An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells.” 2009. Web. 09 Mar 2021.

Vancouver:

Ford L. An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells. [Internet] [Doctoral dissertation]. University of Aberdeen; 2009. [cited 2021 Mar 09]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153044000005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510550.

Council of Science Editors:

Ford L. An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells. [Doctoral Dissertation]. University of Aberdeen; 2009. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153044000005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510550

University of Aberdeen

29. Goonawardena, Anushka V. Cannabinoid effects on hippocampal neurophysiology and mnemonic processing.

Degree: PhD, 2008, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153362110005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499116

► Here we demonstrate that both exogenous and endogenous cannabinoids affect different aspects of learning and memory in the rat. For example, the potent CB₁ receptor… (more)

Subjects/Keywords: 615.1; Cannabinoids; Receptors, Cannabinoid; Endocannabinoids

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Goonawardena, A. V. (2008). Cannabinoid effects on hippocampal neurophysiology and mnemonic processing. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153362110005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499116

Chicago Manual of Style (16^th Edition):

Goonawardena, Anushka V. “Cannabinoid effects on hippocampal neurophysiology and mnemonic processing.” 2008. Doctoral Dissertation, University of Aberdeen. Accessed March 09, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153362110005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499116.

MLA Handbook (7^th Edition):

Goonawardena, Anushka V. “Cannabinoid effects on hippocampal neurophysiology and mnemonic processing.” 2008. Web. 09 Mar 2021.

Vancouver:

Goonawardena AV. Cannabinoid effects on hippocampal neurophysiology and mnemonic processing. [Internet] [Doctoral dissertation]. University of Aberdeen; 2008. [cited 2021 Mar 09]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153362110005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499116.

Council of Science Editors:

Goonawardena AV. Cannabinoid effects on hippocampal neurophysiology and mnemonic processing. [Doctoral Dissertation]. University of Aberdeen; 2008. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153362110005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499116

Mississippi State University

30. Matthews, Anberitha Tyiona. The role of endocannabinoids in atherosclerosis.

Degree: PhD, Veterinary Medicine, College of, 2015, Mississippi State University

URL: http://sun.library.msstate.edu/ETD-db/theses/available/etd-10302015-145832/ ;

► Cardiovascular disease leads in morbidity and mortality in Western societies with no known cure. NADPH oxidase (Nox) contributes to atherosclerosis through the indirect activation… (more)

▼ Cardiovascular disease leads in morbidity and mortality in Western societies with no known cure. NADPH oxidase (Nox) contributes to atherosclerosis through the indirect activation of macrophages leading to the internalization of oxidized low density lipoproteins (oxLDL). Chronic inflammation in activated macrophages contributes to atherosclerosis. Because macrophages are positioned at the cross-roads of lipid metabolism in vessel walls, they are important in the cellular pathology of atherosclerosis. Components of the endocannabinoid (eCB) system are vital to atherosclerotic development, since the eCB system has been found to play an important role in the amelioration of atherosclerosis. The eCB system has several components, including the G-protein-coupled cannabinoid receptors (CB₁ and CB₂); their endogenous ligands, 2-arachidonoylglycerol (2-AG) and anandamide (AEA); and biosynthetic enzymes that produce and degrading these compounds. CB₂ signaling has been shown to upregulate immunoprotective and anti-oxidative pathways, whereas CB₁ signaling has opposite effects. We hypothesized a mechanistic link between scavenger receptor activation and Nox activity, which leads to enhanced 2-AG biosynthesis via a signaling pathway that activates diacylglycerol lipase beta (DAGLB). Activation of CB₂-mediated signaling by enhanced eCB tone can potentially reduce oxidative stress in macrophages. The released 2-AG is subsequently catabolized hydrolytic enzymes, leading to enhanced 2-AGbiosynthesis via activated DAGLB. We first proved that macrophage treated with oxLDL can activate Nox and increase reactive oxygen species production. We used human and mouse macrophages to demonstrate cause and effect. Secondly, we demonstrated that increased levels of superoxide causes enhanced 2-AG biosynthesis within the macrophage, and that upregulation in eCB production is an adaptive response to oxidative stress. Finally, we identified and quantified the serine hydrolases found in smooth muscle cells (SMCs) using an activity-based protein profiling (ABPP)-MudPIT approach that our laboratory has previously done using human macrophages. Additionally, the catabolism of 2-AG by primary SMCs was explored to demonstrate SMCs can hydrolyze 2-AG to its metabolites arachidonic acid and glycerol by the known hydrolytic enzymes. We demonstrated that enhancing endocannabinoid tone within the vessel wall is a valuable strategy to reduce the occurrence of inflammation that leads to atherosclerosis. Advisors/Committee Members: Matthew K. Ross (chair), Stephen B. Pruett (chair), Russell Carr (committee member), G. Todd Pharr (committee member), Larry Hanson (committee member).

Subjects/Keywords: 2-arachidonoylglycerol (2-AG); monocytes/macrophages; NADPH oxidase; atherosclerosis; endocannabinoids; Smooth Muscle Cells

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Matthews, A. T. (2015). The role of endocannabinoids in atherosclerosis. (Doctoral Dissertation). Mississippi State University. Retrieved from http://sun.library.msstate.edu/ETD-db/theses/available/etd-10302015-145832/ ;

Chicago Manual of Style (16^th Edition):

Matthews, Anberitha Tyiona. “The role of endocannabinoids in atherosclerosis.” 2015. Doctoral Dissertation, Mississippi State University. Accessed March 09, 2021. http://sun.library.msstate.edu/ETD-db/theses/available/etd-10302015-145832/ ;.

MLA Handbook (7^th Edition):

Matthews, Anberitha Tyiona. “The role of endocannabinoids in atherosclerosis.” 2015. Web. 09 Mar 2021.

Vancouver:

Matthews AT. The role of endocannabinoids in atherosclerosis. [Internet] [Doctoral dissertation]. Mississippi State University; 2015. [cited 2021 Mar 09]. Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-10302015-145832/ ;.

Council of Science Editors:

Matthews AT. The role of endocannabinoids in atherosclerosis. [Doctoral Dissertation]. Mississippi State University; 2015. Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-10302015-145832/ ;

Open Access Theses and Dissertations