Paraquat exposure increases oxidative stress within the dorsal striatum of male mice with a genetic deficiency in one-carbon metabolism.

07:00 EST 6th February 2019 | BioPortfolio

Summary of "Paraquat exposure increases oxidative stress within the dorsal striatum of male mice with a genetic deficiency in one-carbon metabolism."

Paraquat is a herbicide that is commonly used worldwide. Exposure to paraquat results in Parkinson's disease (PD)-like symptoms including dopaminergic cell loss. Nutrition has also been linked in the pathogenesis of PD, such as reduced levels of folic acid, a B-vitamin and component of one-carbon metabolism. Within one-carbon metabolism, methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-methylTHF). A polymorphism in MTHFR (677 C&cenveo_unknown_entity_wingdings_F0E0;T) has been reported in 5-15% of North American and European human populations. The MTHFR polymorphism is also prevalent in PD patients. The goal of this study was to investigate the impact of paraquat-induced PD-like pathology in the context of reduced levels of MTHFR. Three-month-old male Mthfr+/- mice, which model the MTHFR polymorphism observed in humans, were administered intraperitoneal injections of paraquat (10mg/kg) or saline six times over three weeks. At the end of paraquat treatment, motor and memory function were assessed followed by collection of brain tissue for biochemical analysis. Mthfr+/- mice treated with paraquat showed impaired motor function. There was increased microglial activation within the substantia nigra (SN) of Mthfr+/- mice treated with paraquat. Additionally, all Mthfr+/- mice that were treated with paraquat showed increased oxidative stress within the dorsal striatum, but not the SN. The present results show that paraquat exposure increases PD-like pathology in mice deficient in one-carbon metabolism.


Journal Details

This article was published in the following journal.

Name: Toxicological sciences : an official journal of the Society of Toxicology
ISSN: 1096-0929


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