Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.592875
Title: An evaluation of the potentially neuroprotective properties of cannabinoids in a cell culture model of Parkinson's disease
Author: Zeissler, Marie-Louise
Awarding Body: Exeter and Plymouth Peninsula Medical School
Current Institution: Exeter and Plymouth Peninsula Medical School
Date of Award: 2013
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Abstract:
Parkinson's disease (PD) is a neurodegenerative disorder affecting the dopaminergic neurons within the substantia nigra pars compacta. There is evidence of increased cannabinoid receptor CB 1 signalling as well as exacerbated levels of its endogenous ligands anandamide (AEA) and 2- arachidonoyl glycerol (2-AG), also referred to as endocannabinoids in PD. Due to their ability to dampen synaptic transmission it is currently thought that these changes are part of an autoregulatory response aimed to counteract changes in synaptic transmission caused by the loss of dopamine. However, cannabinoids such as Δ9-tetrahydrocananbinol (Δ9-THC) also have neuroprotective properties and there is evidence for this in models of PD. The aim of this study was to identify whether changes in the endocannabinoid system may occur as a direct response to neurotoxicity and how increased endocannabinoid levels influence cell viability in a 1-methyl-4-phenylpyridium (MPP+) cell culture model of PD. Furthermore this study aimed to identify the mechanism through which Δ9THC is protective. This study discovered that cannabinoid receptor 1 (CB1) expression, as well as AEA metabolism, is increased as a direct response to neuronal injury induced by MPP+. Inhibition of AEA hydrolysis with URB597 was neuroprotective by reducing MPP+ induced oxidative stress in a CB1 receptor independent manner. In contrast, increased 2-AG levels potentiated MPP+ toxicity by elevating oxidative stress.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.592875  DOI: Not available
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