title: Cognitive impairment and increased Aβ levels induced by paraquat exposure are attenuated by enhanced removal of mitochondrial H(2)O(2).
abstract: Pesticide exposure is a risk factor of Alzheimer's disease (AD). However, little is known about how pesticide exposure may promote AD pathogenesis. In this study, we investigated the effects of paraquat pesticide exposure on β-amyloid (Aβ) levels and cognition using wild-type (WT) mice and β-amyloid precursor protein (APP) transgenic mice. Our results showed that wild-type mice and APP transgenic mice after paraquat exposure had increased oxidative damage specifically in mitochondria of cerebral cortex and exhibited mitochondrial dysfunction. Moreover, the elevated mitochondrial damage was directly correlated with impaired associative learning and memory and increased Aβ levels in APP transgenic mice exposed to paraquat. Furthermore, overexpression of peroxiredoxin 3, a mitochondrial antioxidant defense enzyme important for H(2)O(2) removal, protected against paraquat-induced mitochondrial damage and concomitantly improved cognition and decreased Aβ levels in APP transgenic mice. Therefore, our results demonstrate that mitochondrial damage is a key mechanism underlying cognitive impairment and elevated amyloidogenesis induced by paraquat and that enhanced removal of mitochondrial H(2)O(2) could be an effective strategy to ameliorate AD pathogenesis induced by pesticide exposure.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA.
authors.forename: Liuji
authors.initials: L
authors.lastname: Chen
authors.forename: Si-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Ren
authors.initials: R
authors.lastname: Na
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Qitao
authors.initials: Q
authors.lastname: Ran
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D004781:Environmental Exposure; D006540:Herbicides / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D010269:Paraquat / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006540:Herbicides; D006861:Hydrogen Peroxide; D010269:Paraquat