Lifelong Exposure to Polystyrene-Nanoplastics Induces an Attention-Deficit Hyperactivity Disorder-like Phenotype and Impairs Brain Aging in Mice

The accumulation of plastic waste in the environment, breaking down into micro- and nanoplastics, poses significant threats to ecosystem and human health. Plastic particles have been detected in human blood, urine, and placental tissue, indicating widespread exposure. While their long-term health impacts remain unclear, developing brains, especially in fetuses and children, may be vulnerable, potentially resulting in behavioral changes or neurodevelopmental disorders. This study explores the effects of chronic exposure to 23-nm polystyrene nanoplastics at 10 µg/day/kg in wild-type mice across life stages, using exposure levels reflective of human reality. Maternal exposure disrupted critical developmental milestones in pups. In adulthood, exposed mice exhibited Attention-Deficit Hyperactivity Disorder (ADHD)-like traits, including hyperactivity, increased risk-taking behaviors, and impaired motor learning and executive functions. In aging mice, exposure was associated with a lower epileptic threshold, with developing seizures. These behavioral changes were linked to altered gene and synaptic protein expression associated with ADHD and epilepsy. At the cellular level, lifelong nanoplastic exposure caused lysosomal dysfunctions and increased lipofuscin accumulation, indicative of accelerated brain aging. These findings align with the growing prevalence of ADHD and epilepsy in humans, particularly children and the elderly, emphasizing the urgent need to address plastic pollution and its health implications.