Title : Prenatal lead exposure as a catalyst for neurodevelopmental reprogramming in the offsprings
Abstract:
Prenatal lead toxicity remains a critical public health issue due to its lasting detrimental effects on fetal brain development. Lead mimics calcium ions enabling it to traverse both the placental and blood-brain barriers thereby inducing neurodevelopmental alterations. This study examines that impact of prenatal lead exposure on neurobehavioral phenotypes, brain morphology, neurotransmitter dynamics and gene expression in F1 progeny. Female SD rats received lead nitrate at 2mg/kg BWt through drinking water spanning from preconception to weaning period. Significant lead accumulation was confirmed in both blood and brain of F1 offspring through ICPMS. Behavioral assays evaluating anxiety, social interaction and repetitive behavior revealed increased anxiety like behavior, impaired social interaction and increased repetitive actions in lead-exposed progeny. Histological analysis with Golgi-Cox and Sholl analysis demonstrated reduced dendritic complexity (p<0.01) indicating disrupted neuronal connectivity. Biochemically, acetylcholinesterase activity was reduced (p<0.05), dopamine levels exhibited significant elevation and variability (p<0.05) and glutamate but not GABA levels were significantly altered as measured by HPLC. At molecular level, key neurodevelopmental genes associated with ASD and synaptic functions namely Ctnnb1, Cacna1c and Shank3 were significantly dysregulated in exposed animals (p<0.05). These dysregulations provide evidence for the urgency of targeted preventive interventions during critical periods of brain development.
