Expression of the NR2A and 2B Subunits of N-Methyl-D-aspartate Receptors in Hypoxic Neonatal Rat Hippocampus

ABSTRACT

PURPOSE: The developing brain has been reported to be extremely susceptible to toxicity of ischemia and/or hypoxia during a restricted developmental period. Hippocampal neuronal cell death is a typical type of perinatal hypoxic brain lesion and often coexists with other forms of cerebral hypoxic injuries. In the present study, we examined whether transcriptional changes of NR2A and NR2B subunits of the N-Methyl-D-aspartate(NMDA) receptors related to the neuronal cell death to hypoxic toxicity are involved in developing neurons in the hippocampus. METHODS: We examined the lesion produced by in vivo direct exposure of 92% N2 and 8% O2 for 2 hours at postnatal day 7. Hippocampal sections from the 7th and 14th days after hypoxia were obtained, and the amount of the NR2A and NR2B mRNA subunits were measured by in situ hybridization using the antisense probe to the NR2A and NR2B subunits. To determine the effects of molecular changes of NMDA receptor subunits, morphological changes of neurons and/or accompanying astrocytosis were evaluated by H&E and immunohistochemical stain. RESULTS: Fourteen days after hypoxia, the expression of NR2B significantly increased whereas NR2A showed distinct reduction compared with that of control rat pups. At this time, unexpectedly, neurons in CA3 region showed prominant reduction of the actual numbers and accompanied reactive astrocytosis. CONCLUSION: Alteration of NR2A and NR2B expression to hypoxic insults, suggest the possibility that changes of the NR2 subunits which can alter the function of the NMDA receptor play a crucial role in the occurrence of developmentally specific hippocampal neuronal injury.