Early-life lead exposure induces long-term toxicity in the central nervous system: From zebrafish larvae to juveniles and adults

Lead induced neurotoxicity has been extensively investigated. However, the potential connections between early-life lead exposure and the frequently observed aberrant neurobehavior in juveniles and adults remain unclear. In this study, zebrafish model was used to explore the immediate and long-term effects of early-life exposure to environmental levels of lead on the central nervous system, and the cellular and molecular mechanisms underlying the consequent abnormal neurobehavior. Lead exposed zebrafish larvae exhibited neurologic damage and defective neurobehavior. Consistent with clinical studies, despite being raised in lead-free conditions, the juvenile and adult fish experienced lead exposure earlier, presented ADHD-like symptoms, and the adult fish exhibited remarkably affected vitality and shoaling behavior. Their anxiety levels were elevated, whereas their social interaction, as well as learning and memory were strongly depressed. The expression profiles of key genes involved in neurodevelopment and neurotransmitter systems were significantly modulated, in similar patterns as in the larval stage. Notably, the density of neurons was decreased and varicosities in neuronal axons were frequently observed in the lead-exposed groups. It's tempting to speculate that the disruption of early neurodevelopment as well as the prolonged modulation of neuromorphic and neurotransmitter systems contribute to the lead-induced neurobehavioral disorders observed in juveniles and adulthood.