Thesis
French
ID: <
http://hdl.handle.net/20.500.11794/23326>
Abstract
Table of Honour of the Faculty of Higher and Post-doctoral Studies, 2011-2012 Parkinson’s disease (MP), a neurodegenerative disorder, affects 1 % of the population over 65 years of age and is defined, inter alia, by a marked loss of dopaminergic neurones of the black compacta pars (SNPC) and consequently a drastic drop in dopamine levels is observed in Striatum. The post-mortem presence of Lewy bodies, mainly formed of aggregated a-synucleine, is also a characteristic feature of the disease. Several issues associated with MP, some of which are considered major, may hinder the discovery of treatments. First, the causes leading to the degeneration and initiation of synucleinopathy remain largely unknown, despite the discovery of genetic mutations specific to a subgroup of patients and the identification of environmental factors through epidemiological associative studies. A second obstacle is the lack of biomarkers to diagnose the disease earlier in its development, as the pathology becomes apparent when around 6070 % of neurons are degenerated. As a result of these difficulties, MP currently only has symptomatological therapeutic options, no treatment is available to change the evolving course of the degenerative process started several years before diagnosis. My doctoral project is therefore part of a global theme targeting several aspects of the above issue. As part of a nutraceutical approach through the use of omega-3 fatty acids, we have investigated the neuroprotective effect of Omega- fatty acids and the mechanisms of action underpinning this beneficial effect. The effects of omega-3 fatty acids have also been investigated from a non-nutritional perspective, by the endogenous transgenic conversion of omega-6 to omega-3 in Fat-1 mice. Conversely, we also looked at the consequences of a diet providing a high fat intake in a Parkinsonian mouse model. Briefly, our studies have identified neuroprotective properties to omega-3 fatty acids following long-term treatment in an animal model of MP in addition to combining adverse effects of a fatty rich diet and depleted in omega-3 fatty acids in the same animal model. These conclusions underline the important contribution of nutrition to the pathology and suggest that high fat and low omega-3 intake could be a risk factor for MP. Although our results demonstrate a protective effect of omega-3 fatty acids, a critical question remains about their neurorestoration properties. In this respect, the investigation of therapeutic capabilities is ongoing in order to assess the potential of omega-3 fatty acids following the induction of dopaminergic depletion via the administration of MPTP neurotoxin in mice.