Neonatal toluene exposure alters N-methyl-D-aspartate receptor subunit expression in the hippocampus and cerebellum in juvenile rats

Recent evidence indicates that toluene is a non-competitive inhibitor of N-methyl-D-aspartate (NMDA) receptor-mediated synaptic currents. The NMDA receptor plays a major role in neuronal development and differentiation. The present study characterized the long-term effects of toluene exposure during synaptogenesis on the expression of NMDA receptor subunits (NR1, NR2A and NR2B). Neonatal rats were administered toluene (500 mg/kg, ip) daily over postnatal days (PN) 4-9. The expression of NMDA receptor subunits in rat brain was measured on PN 30. Western blot analysis demonstrated that toluene exposure significantly increased NR2A expression in the hippocampus and cerebellum. Inummohistochemical results indicated that the increased NR2A expression is mainly in hippocampal CA1-stratum oriens, CA1-stratum radiatum, CA1-lacunosm molecular, CA2-stratum oriens, and dentate gyrus-molecular layer and the cerebellar Purkinje cell layer, respectively. In contrast, the levels of NR2B in the toluene-exposed rats were decreased in the molecular layer. These results suggest that the region-specific changes in the expression of NMDA receptor subunits may be related to the neurobehavioral dysfunction following toluene exposure during synaptogenesis. (C) 2004 Elsevier Ltd. All rights reserved.