The purpose of the present study was to examine the differential effects of lead (Pb) exposure on the expression of specific NMDA receptor subunit mRNAs on the hippocampal cells depending on the neuronal developmental stage.

Expression of the NR2A and NR2B subunits of the NMDA receptors mRNA on the hippocampal neurons was measured by in situ hybridization in the control and Pb treated groups. Pb-treated and NMDA cytotoxicity was assessed by morphological examination and LDH measurements.

Hippocampal NR2A subunit mRNA expression was gradually increased with increasing age, and was significantly decreased after Pb exposure. The expression of NR2B subunit mRNA was not changed during development in the rat hippocampus and the developmental effect of Pb exposure on NR2B expression was minimal. These results indicate that chronic Pb exposure may decrease the levels of NR2A-containing NMDA receptors and may thereby alter normal synaptic signal transmission. Pb or NMDA-induced cytotoxicity in vitro differed significantly between the immature and the mature hippocampal cells.

This study demonstrates that chronic Pb exposure during brain development alters the levels of specific NMDA receptor subunit mRNA in the rat hippocampus. These results suggest that chronic Pb exposure may attenuate the precise neuronal synaptic transmission through the differential alteration of the composition of the NMDA receptor subunit on the hippocampus depending on neuronal developmental stage.