Journal article
N. Jadavji, Lauren K. Murray, Joshua T. Emmerson, Chris Rudyk, S. Hayley, Patrice D. Smith
Toxicological Sciences, 2019
Toxicological Sciences, 2019
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Jadavji, N., Murray, L. K., Emmerson, J. T., Rudyk, C., Hayley, S., & Smith, P. D. (2019). Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-carbon Metabolism. Toxicological Sciences.
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Jadavji, N., Lauren K. Murray, Joshua T. Emmerson, Chris Rudyk, S. Hayley, and Patrice D. Smith. “Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-Carbon Metabolism.” Toxicological Sciences (2019).
MLA
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Jadavji, N., et al. “Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-Carbon Metabolism.” Toxicological Sciences, 2019.
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@article{n2019a,
title = {Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-carbon Metabolism.},
year = {2019},
journal = {Toxicological Sciences},
author = {Jadavji, N. and Murray, Lauren K. and Emmerson, Joshua T. and Rudyk, Chris and Hayley, S. and Smith, Patrice D.}
}
Abstract
Paraquat is an 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. A polymorphism in MTHFR (677 C&→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 (10 mg/kg) or saline 6 times over 3 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.