Age-dependent Effect Imposed by Rotenone Exposure

Background: The increasing awareness that environmental exposure may lead to sporadic neurological disorders has implicated rotenone to the etiology of some neurodegenerative diseases. However, the risk associated with rotenone toxicity remains controversial as a limited amount of research has studied its effects on brain health. Objectives: This work assessed the risk of rotenone exposure to mice of different ages, gender, and duration by examining in vivo effects on brains. Methods: Using a mouse model, the impact of rotenone exposure was determined by analyzing the cellular phenotype in the murine brain. Results: Our results highlight the neurological susceptibility to long-term rotenone exposure in younger ages. For such, younger mice exhibit seizures and convulsions, resulting in shorter lifespan. At the cellular level, rotenone exposure specifically alters the migrating neuroblast populations in the dentate gyrus and causes disorganized pyramidal neurons in the CA3 within the hippocampus. Our findings, albeit the absence of transgenerational inheritance, demonstrated age-related outcomes from rotenone exposure. Discussion: We demonstrated that rotenone exposure specifically influences the population of neuroblasts and pyramidal neurons residing in the hippocampus, a brain region important for learning/memory and associated with convulsive seizure. Our understanding of how exactly rotenone affected region-specific neuronal cells and the molecular mechanism behind exposure risk is still limited. From the perspective of public health, our in vivo study highlights age-related susceptibility to rotenone toxicity. Future investigations in environmental epidemiology should determine whether age and duration of exposure to rotenone in human subjects pertains to the development of seizures or other neurological abnormalities over time.