Early-Life Exposure to Paraquat Aggravates Sex-Specific and Progressive Abnormal Non-Motor Neurobehavior in Aged Mice

Early-life exposure to environmental neurotoxicants is known to have lasting effects on organisms. In this study, we aim to investigate the impacts of PQ exposure during early developmental stages and adult re-challenge in aged mice on non-motor neurobehavior. Two mouse models, which were exposed once during early life stage and re-exposure at adulthood, were created to explore the long-term effects of PQ on non-motor neurobehavior. As the results showed, early-life exposure to PQ caused impairment in working memory and cognitive ability in aged male mice, but not in female mice, exhibiting a sex-specific impairment. Moreover, male mice that were re-challenged with PQ at adulthood following early-life exposure also exhibited non-motor neurobehavioral disorders. Notably, re-exposure to PQ exacerbated neurobehavioral disorders and anxiety levels compared to single exposure during different life stages. Collectively, early-life exposure to PQ can result in irreversible impairments in non-motor neurobehavior and increase susceptibility to subsequent insults in male mice, but not in female mice, suggesting greater sensitivity in male rodents to PQ-induced non-motor neurobehavioral deficits.