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You searched for +publisher:"University of New South Wales" +contributor:("Karl, Tim, Neuroscience Research Australia"). Showing records 1 – 3 of 3 total matches.

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University of New South Wales

1. Cheng, David. The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease.

Degree: Medical Sciences, 2014, University of New South Wales

Background: Alzheimer’s disease (AD) is the most prevalent form of dementia, characterised by amyloid-β (Aβ) plaques and neurofibrillary tangles. Other processes include neurodegeneration, neuroinflammation, neurotoxicity and oxidative stress. Patients suffer from widespread behavioural and cognitive decline, including social withdrawal and memory loss. Therapeutic options are limited and efficacy is poor, prompting the need for other potential therapeutic avenues. In particular, emerging studies implicate the non-psychoactive phytocannabinoid, cannabidiol (CBD), as a potential therapeutic option due to its anti-inflammatory, antioxidant and neuroprotective properties that may be relevant for AD. In vitro evidence shows CBD prevents Aβ-induced neurotoxicity, neuroinflammation, cell death, tau protein hyperphosphorylation and promotes adult hippocampal neurogenesis.Method: The aim of my thesis was to evaluate the therapeutic potential of CBD in a genetic mouse model of AD. I established novel behavioural phenotypes including social recognition and spatial memory deficits for the APPSwe/PS1∆E9 (APPxPS1) double transgenic mouse model and determined the in vivo effects of CBD treatment on AD mice. For this, I assessed the ability of CBD to remedy or prevent the development of cognitive deficits and brain pathophysiology of APPxPS1 mice by daily treatment with either vehicle or CBD (20 mg/kg) for: a) 3 weeks post-onset (intraperitoneal administration), or b) 8 months (oral administration) prior to the onset of AD. Treatment was followed by comprehensive cognitive testing and AD-relevant biochemical analyses. Results: APPxPS1 mice exhibited cognitive deficits in spatial memory and social recognition. CBD treatment prevented and reversed recognition memory deficits of APPxPS1 transgenic mice. Biochemical analyses implicated that the therapeutic potential of CBD might be related to its impact on neuroinflammation and dietary phytosterols.Conclusions: APPxPS1 transgenic mice demonstrated novel cognitive deficits relevant for AD. These deficits could be prevented and ameliorated by CBD treatment potentially via its anti-inflammatory actions and its impact on dietary phytosterols. CBD possesses therapeutic potential for the treatment of AD symptomatology and should be evaluated further in clinical trials. Advisors/Committee Members: Karl, Tim, Neuroscience Research Australia, Faculty of Medicine, UNSW, Garner, Brett, Illawarra Health and Medical Research Institute, University of Wollongong.

Subjects/Keywords: APPSwe/PS1dE9 trangenic mice; Alzheimer's disease; Cannabidiol; Amyloid load; Behaviour; Cholesterol; Neuroinflammation; Oxidative stress; Phytosterol; Social recognition memory

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APA (6th Edition):

Cheng, D. (2014). The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53839 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12526/SOURCE02?view=true

Chicago Manual of Style (16th Edition):

Cheng, David. “The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease.” 2014. Doctoral Dissertation, University of New South Wales. Accessed August 17, 2019. http://handle.unsw.edu.au/1959.4/53839 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12526/SOURCE02?view=true.

MLA Handbook (7th Edition):

Cheng, David. “The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease.” 2014. Web. 17 Aug 2019.

Vancouver:

Cheng D. The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease. [Internet] [Doctoral dissertation]. University of New South Wales; 2014. [cited 2019 Aug 17]. Available from: http://handle.unsw.edu.au/1959.4/53839 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12526/SOURCE02?view=true.

Council of Science Editors:

Cheng D. The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease. [Doctoral Dissertation]. University of New South Wales; 2014. Available from: http://handle.unsw.edu.au/1959.4/53839 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12526/SOURCE02?view=true


University of New South Wales

2. Olaya, Juan. Neurobiological investigation of the Neuregulin 1 gene and Neuregulin 1 type III overexpression in the pathophysiology of schizophrenia.

Degree: Psychiatry, 2019, University of New South Wales

Schizophrenia is a severe psychiatric disorder where patients suffer from hallucinations, delusions, social deficits and cognitive impairments. Perturbations in the maturation, expression and function of inhibitory interneurons have been detected in the brains of schizophrenia patients and are thought to contribute to the social and cognitive impairments found in the disease, however the mechanism behind this interneuron pathology is underexplored. Schizophrenia-associated gene, Neuregulin 1 (NRG1), encodes for numerous NRG1 protein isoforms that uniquely mediate various aspects of inhibitory interneuron migration and function. Elevated levels of the NRG1 type III isoform have been observed in the forebrain of schizophrenia patients carrying NRG1 HapICE alleles, however the role of this upregulated isoform in the cortical neuropathology found in schizophrenia is not known. This thesis sought to assess whether carrying NRG1 HapICE alleles was associated with increased inhibitory interneuron pathology in those with schizophrenia, and whether overexpression of NRG1 type III, in the murine forebrain, could result in inhibitory interneuron pathology and impair cognition akin to schizophrenia. I showed that Nrg1 type III overexpression caused an increase in forebrain calbindin mRNA and accompanying impairments social functioning and cognitive performance, particularly for tasks requiring hippocampal-dependent memory. This led me to examine the possible mechanisms by which Nrg1 type III overexpression could impair hippocampal-dependent memory. Using a discovery- driven approach, I identified novel signalling pathways which appear to be dysregulated by Nrg1 type III overexpression, including transcripts associated withinsulin-like growth factor signalling, neuroinflammation and adult hippocampal neurogenesis. Finally, I showed for the first time that increasing NRG1 HapICE risk load is associated with greater forebrain inhibitory interneuron pathology, including reduced somatostatin and increased calbindin mRNA cortical expression in those with schizophrenia. In sum, I have shown that elevated NRG1 type III mRNA in the forebrain of NRG1 HapICE schizophrenia patients may contribute towards the exacerbated of some inhibitory interneuron pathology found in schizophrenia patients carrying NRG1 HapICE risk alleles, as well as novel mechanisms by which NRG1 type III overexpression could impair cognition in patients carrying these risk alleles. These findings may assist us in selecting targeted treatments towards this subset of individuals with schizophrenia. Advisors/Committee Members: Shannon Weickert, Cynthia, Psychiatry, Faculty of Medicine, UNSW, Karl, Tim, Neuroscience Research Australia, Purves-Tyson, Tertia, Psychiatry, Faculty of Medicine, UNSW, Sinclair, Duncan, Neuroscience Research Australia.

Subjects/Keywords: Transgenic mouse; Schizophrenia; Neuregulin 1

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

APA (6th Edition):

Olaya, J. (2019). Neurobiological investigation of the Neuregulin 1 gene and Neuregulin 1 type III overexpression in the pathophysiology of schizophrenia. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/61976

Chicago Manual of Style (16th Edition):

Olaya, Juan. “Neurobiological investigation of the Neuregulin 1 gene and Neuregulin 1 type III overexpression in the pathophysiology of schizophrenia.” 2019. Doctoral Dissertation, University of New South Wales. Accessed August 17, 2019. http://handle.unsw.edu.au/1959.4/61976.

MLA Handbook (7th Edition):

Olaya, Juan. “Neurobiological investigation of the Neuregulin 1 gene and Neuregulin 1 type III overexpression in the pathophysiology of schizophrenia.” 2019. Web. 17 Aug 2019.

Vancouver:

Olaya J. Neurobiological investigation of the Neuregulin 1 gene and Neuregulin 1 type III overexpression in the pathophysiology of schizophrenia. [Internet] [Doctoral dissertation]. University of New South Wales; 2019. [cited 2019 Aug 17]. Available from: http://handle.unsw.edu.au/1959.4/61976.

Council of Science Editors:

Olaya J. Neurobiological investigation of the Neuregulin 1 gene and Neuregulin 1 type III overexpression in the pathophysiology of schizophrenia. [Doctoral Dissertation]. University of New South Wales; 2019. Available from: http://handle.unsw.edu.au/1959.4/61976


University of New South Wales

3. Bhatia, Surabhi. Elucidation of apolipoprotein D lipid antioxidant mechanism and its relevance to Alzheimer’s disease.

Degree: Medical Sciences, 2013, University of New South Wales

Apolipoprotein D (apoD) is a widely expressed, multifunctional apolipoprotein known for its lipid antioxidant properties in the brain. It is upregulated under oxidative stress conditions including aging and in neurodegenerative diseases. The mechanism of lipid antioxidant function of apoD and reasons for its upregulation in neurodegenerative diseases is unknown. Hence the aim of this thesis was to study the lipid antioxidant mechanism of apoD and its relevance to the most common form of neurodegenerative disease, Alzheimer's disease (AD). To study the mechanism of lipid antioxidant function of apoD, the interaction of recombinant apoD and its methionine mutants (methionine substituted with alanine) with hydroperoxyeicosatetraenoic acids (HpETE) were analysed using HPLC and amino acid analysis techniques. The Met93 residue of apoD was required for the reduction of HpETE to its hydroxyeicosatetraenoic acid derivative (HETE), and this reaction was concomitant with the formation of methionine sulfoxide (MetSO). Western blot analysis revealed that the oxidation of apoD Met residues causes apoD aggregation. This was supported by in-silico simulations which indicated that the oxidation of Met93 is accompanied by destabilisation of a surface-exposed hydrophobic domain that is predicted to increase the propensity for apoD to self-associate. Furthermore, the link between lipid peroxidation, apoD expression and aggregation of apoD was analysed with disease progression in AD brain using High performance liquid chromatography (HPLC), Gas chromatography–Mass spectrometry (GC-MS) and Western blot analysis. Lipid conjugated dienes and F2- isoprostanes, measured as markers of lipid peroxidation, were increased in later stages of the disease. The expression of apoD also increased with disease progression and formation of apoD dimers were detected in the insoluble protein fraction of the hippocampus in late stage AD patients. Moreover, the formation of apoD dimers is closely correlated to lipid conjugated diene levels in AD hippocampus. In summary, the Met93 residue of apoD is required for the lipid antioxidant function of apoD. Furthermore, oxidation of methionine residues, particularly Met93, results in self-association of apoD and production of a stable dimer that is observed in vitro and in post-mortem brain derived from late stage AD cases. The increase in apoD expression with disease progression, similar to other antioxidants, suggests that apoD has the potential to reduce lipid peroxidation in AD brain. However, its self-association in late disease stages may prevent it from acting as a lipid antioxidant. Advisors/Committee Members: Garner, Brett, University of Wollongong, Illawarra Health and Medical Research Institute, Karl, Tim, Neuroscience Research Australia, Faculty of Medicine, UNSW, Kim, Scott, Neuroscience Research Australia, Faculty of Medicine, UNSW.

Subjects/Keywords: Methionine residues; Apolipoprotein D; Lipid antioxidant; Alzheimer's disease

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

APA (6th Edition):

Bhatia, S. (2013). Elucidation of apolipoprotein D lipid antioxidant mechanism and its relevance to Alzheimer’s disease. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52742 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11415/SOURCE01?view=true

Chicago Manual of Style (16th Edition):

Bhatia, Surabhi. “Elucidation of apolipoprotein D lipid antioxidant mechanism and its relevance to Alzheimer’s disease.” 2013. Doctoral Dissertation, University of New South Wales. Accessed August 17, 2019. http://handle.unsw.edu.au/1959.4/52742 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11415/SOURCE01?view=true.

MLA Handbook (7th Edition):

Bhatia, Surabhi. “Elucidation of apolipoprotein D lipid antioxidant mechanism and its relevance to Alzheimer’s disease.” 2013. Web. 17 Aug 2019.

Vancouver:

Bhatia S. Elucidation of apolipoprotein D lipid antioxidant mechanism and its relevance to Alzheimer’s disease. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2019 Aug 17]. Available from: http://handle.unsw.edu.au/1959.4/52742 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11415/SOURCE01?view=true.

Council of Science Editors:

Bhatia S. Elucidation of apolipoprotein D lipid antioxidant mechanism and its relevance to Alzheimer’s disease. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/52742 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11415/SOURCE01?view=true

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