Lead exposure during development alters synaptic organization and protein expression in rat hippocampus

Lead (Pb) is a well-established environmental neurotoxicant known to impair cognitive, sensory, and behavioral functions. Developmental exposure to Pb induces irreversible morphological and functional alterations in the central nervous system. In this study, we investigated the impact of early-life Pb exposure on anxiety-like behaviour, hippocampal structure and protein expression in rats. Neonatal rats were exposed to 100 ppm Lead acetate via maternal lactation from postnatal day (PND) 1-21. Behavioral assessment using the light-dark box test revealed a significant reduction in latency to enter the dark chamber in Pb-exposed animals, indicative of increased anxiety-like behavior. Nissl staining of hippocampal sections revealed a significant reduction in neuronal density within the CA1 subregion of Pb-exposed animals. Detailed morphometric analysis of CA1 pyramidal neurons showed dendritic hypertrophy accompanied by a marked decrease in spine density in both apical and basal dendrites. Proteomic profiling using high-resolution mass spectrometry identified 6780 proteins, of which 190 were significantly altered (p < 0.05) between Pb-exposed and control groups. Among these, 31 proteins were found to be dysregulated in the hippocampus following Pb exposure. Proteomic data are publicly available via ProteomeXchange (identifier: PXD064482). Furthermore, we validated the proteomic data by performing Western blot analysis for four dysregulated proteins. Collectively, these findings demonstrate that early-life Pb exposure elicits profound structural and molecular alterations in the hippocampus, accompanied by behavioral dysfunction. These changes may underlie the enduring neurobehavioral impairments associated with developmental Pb neurotoxicity.