Possible regulation by N-methyl-d-aspartate receptors of proliferative progenitor cells expressed in adult mouse hippocampal dentate gyrus.

An immunohistochemical technique was employed to analyze mechanisms underlying modulation by N-methyl-d-aspartate (NMDA) receptors of proliferation of neural progenitor cells in adult mouse brain. The systemic administration of NMDA at 100 mg/kg resulted in marked expression of c-Fos, Fra-2 and c-Jun proteins in the granule cell layers of the dentate gyrus in murine hippocampus 2 h later, followed by a significant reduction of the incorporation of 5-bromo-2'-deoxyuridine (BrdU) in a manner sensitive to the antagonist dizocilpine 2 days after administration. The administration of NMDA also suppressed constitutive expression of both nestin and proliferating cell nuclear antigen (PCNA) in the dentate granule cells 2 days later, without markedly affecting cell viability for up to 8 weeks after administration. In the subventricular zone and olfactory bulb, however, NMDA failed to affect either the incorporation of BrdU or the expression of nestin and PCNA. The NR1 subunit was highly expressed in the dentate gyrus in addition to the stratum oriens in the hippocampus, but not in the subventricular zone and olfactory bulb. These results suggest that NMDA receptors may play a role crucial for maintenance of the integrity and function of proliferative neural progenitor cells through expression of the nuclear transcription factor activator protein-1 in granule cells of the dentate gyrus in adult mouse brain.