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The Journal of Neuroscience, March 1, 2000, 20(5):1666-1674

Declines in mRNA Expression of Different Subunits May Account for Differential Effects of Aging on Agonist and Antagonist Binding to the NMDA Receptor

Kathy R. Magnusson

Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523-1670

The purpose of the present study was to determine whether some of the age-related changes that occur in binding to the NMDA receptor complex can be accounted for by changes in subunit expression during the aging process. In situ hybridization for the NMDA subunits 1, 1, and 2, and receptor autoradiography, using the agonist glutamate and the competitive antagonist [(±)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (CPP), were performed on sections from C57Bl/6 mice representing three different age groups (3, 10, and 30 months of age). There was a significant overall decrease between 3 and 30 month olds in the density of mRNA for the 1 subunit in the cortex and hippocampus, but only a few individual brain regions exhibited significant declines. The mRNA for the 2 subunit was significantly decreased in a majority of cortical regions and in the dentate granule cells. Emulsion analysis indicated that the change in the density of 2 subunit mRNA in the inner frontal cortex was primarily attributable to a decrease in the amount of messages per cell. Age-related changes in mRNA density of the 2 subunit correlated with changes in NMDA-displaceable [³H]glutamate binding, and mRNA density changes in the 1 subunit showed a significant relationship with changes in [³H]CPP binding in the 30-month-old mice. These results suggest that changes during aging in the expression of different subunits of the NMDA receptor may account for the differential effects of aging on agonist versus antagonist binding to the NMDA binding site.

Key words: NMDA receptors; NMDA subunits; in situ hybridization; glutamate; aging; mRNA

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2051666-09$05.00/0

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