The Impact of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in a Paraquat Mouse Model of Parkinson’s Disease

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Murray, Lauren Krystina




The cause of Parkinson's disease (PD) remains unknown. Environmental toxicants such as paraquat have been linked to the characteristic dopaminergic (DA) neurodegeneration in the substantia nigra (SN); nutrition may also play a role. A common polymorphism (677C>T) in methylenetetrahydrofolate reductase (MTHFR), a folic acid metabolism enzyme, is associated with increased PD incidence. Using a mouse model that mimics this polymorphism, this study aimed to determine whether MTHFR deficiency leads to enhanced degeneration in a paraquat PD model. Male 3-month-old Mthfr+/+ and Mthfr+/- mice received paraquat or saline injections. Mthfr+/- mice demonstrated motor and a trend for memory impairment compared to Mthfr+/+ mice. No differences in SN DA neuron numbers or antioxidant activity were seen, however, increased oxidative stress and antioxidant activity were observed within the dorsal striatum of Mthfr+/- mice. These results suggest potential enhanced vulnerability to paraquat due to MTHFR deficiency through changes in such processes within this region.






Carleton University

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