The effects of eicosapentaenoic acid (EPA) treatments on the oxidative stress mechanism in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced Parkinson's disease models

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system (CNS) and characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the striatum. Oxidative stress may contribute to the pathogenesis of the disease. Omega (n)-3 fatty acid, eicosapentaenoic acid (EPA), as antioxidant, may have the potential effect to prevent PD via modulating the oxidative stress.To explore the oxidative stress mechanisms and the changes of fatty acids in PD and the modulatory function of EPA, three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD models, cellular model, mouse brain slice model and chronic model were created. The general hypothesis of this thesis was that MPTP may increase oxidant production and destroy the balance between the oxidative and anti-oxidative systems, which may contribute to the reduction of mitochondrial activity in the cellular model of PD and contribute to the changes in the brain fatty acid profile in the animal models.Mitochondrial dehydrogenase activity was tested by MTT assay. Oxidants were measured by 2',7'-dichlorofluo-rescindiacetate (DCF-DA) and 4,5-Diaminofluorescein diacetate (DAF-DA). Quantitative PCR was applied to measure antioxidants and pro-oxidant enzyme gene expressions. Protein expression of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) was measured by Western blot. Antioxidant glutathione (GSH) level was measured by a GSH assay kit. Fatty acid contents in the mouse brain were investigated by gas chromatography (GC).Source: Masters Abstracts International, Volume: 48-06, page: 3539