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

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.