Alterations of Synaptic Proteins in the Hippocampus of Mouse Offspring Induced by Developmental Lead Exposure

Lead exposure can cause cognitive dysfunction in children, thus it still raises important public health concerns in China and other countries. However, the underlying molecular mechanisms are still not well defined. In this study, we aimed to elucidate the mechanisms underlying lead neurotoxicity by focusing on alterations of synaptic proteins in the mouse hippocampus at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0, and 2.0 g/L lead via drinking water from the first day of gestation until postnatal day (PND) 40. Synaptic ultrastructure and expressions of postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS) and synaptophysin (SYP) at both protein and gene levels in the hippocampus were analyzed. The results revealed that developmental lead exposure caused a diminished postsynaptic density in the hippocampus. Moreover, the protein levels of PSD-95, nNOS, and SYP decreased significantly due to developmental lead exposure. On the other hand, the messenger RNA (mRNA) levels of PSD-95 and SYP decreased significantly in PND 40 mice exposed to lead. Collectively, developmental lead exposure might result in decreased protein and gene expressions of both presynaptic and postsynaptic proteins. Our findings raised a possibility that alterations of synaptic proteins in the hippocampus induced by lead exposure at the early life might serve an important role for the subsequent intellectual impairments, e.g., deficits in spatial learning and memory ability at later ages shown in our recently published paper.