CHANGES IN NMDA RECEPTOR NITRIC-OXIDE SIGNALING PATHWAY IN THE BRAIN WITH AGING

The N-methyl-D-aspartate (NMDA) receptor/nitric oxide (NO) signaling p athway plays an important role in neuronal plasticity. Previous studie s with in vitro autoradiography showed that the number of NMDA recepto r/ion channel complexes in the cerebral cortex and hippocampus is decr eased by aging. Confocal laser scanning microscopy reveals circuit-spe cific alterations of NMDA receptor subunit 1 in the dentate gyrus of a ged monkeys. Histochemistry for NADPH diaphorase (NADPH-d), a marker f or neurons containing NO synthase (NOS), reveals that the number of NA DPH-d-positive neurons in the cerebral cortex and striatum is signific antly reduced from that in young rats. In the hippocampus, no age-rela ted changes in NADPH-d staining are reported, while in situ hybridizat ion histochemistry indicates an increase in the level of mRNA for neur onal NOS. NOS activity in the brain also appears to decrease with agin g. These results suggest that the function of the NMDA receptor/NO sig naling pathway in the brain is impaired by aging, and that dysfunction of this signaling pathway may underlie aging-associated memory impair ment in rats. (C) 1998 Wiley-Liss, Inc.