Behavioral and neurochemical changes in mice induced by low-level lead exposure: Implications for ADHD and conduct disorders

Lead (Pb) exposure in children and adolescents poses a significant public health risk due to its potential neurotoxic effects. While high-level Pb exposure is known to impair learning and cognition, the behavioral and molecular consequences of low-level Pb exposure during developmental periods remain poorly understood. This study examined behavioral and neurochemical changes in mice exposed to Pb acetate exposure via drinking water from 4 to 8 weeks of age, corresponding to the juvenile through early adult developmental stages in mice. Mice exposed to 30 mg/L resulting in blood lead levels (BLLs) of 1.26 ± 0.089 µg/dL, while the 300 mg/L group, included as a neurotoxic reference, displayed BLLs exceeding 10 μg/dL. Behaviorally, exposure to 30 mg/L Pb did not affect locomotor activity, however, mice exposed to 300 mg/L exhibited hyperactivity and impaired nesting. Notably, impulsive and compulsive behaviors were significantly altered even at 30 mg/L. Neurochemically, qPCR and Western blotting analysis revealed downregulation of DOPA decarboxylase (Ddc), an enzyme crucial for dopamine synthesis, alongside decreased dopamine levels in the striatum. Pb exposure also disrupted striatal dopaminergic signals, including tyrosine hydroxylase (TH) and dopamine D2 receptors (D2R). These findings suggest that even low-level Pb exposure can lead to behavioral dysfunctions by disrupting striatal dopaminergic signaling, highlighting a previously underexplored mechanism of Pb neurotoxicity. • Low blood lead levels (BLLs) during neurodevelopment induce neurotoxic effects and behavioral changes in mice. • Developmental Pb exposure increases impulsivity and compulsive-related behaviors. • Pb disrupts striatal dopamine signaling by inhibiting DOPA decarboxylase and altering tyrosine hydroxylase (TH and D2R) expression. • Findings support the notion that no safe threshold exists for lead exposure during brain development.