REGIONAL DIFFERENCES IN AGE-RELATED CHANGES IN NMDA RECEPTOR EXPRESSION WITHIN THE PREFRONTAL CORTEX AND HIPPOCAMPUS
K.R. Magnusson*, L. Bai, D. Kresge, and J. Supon
Department of Anatomy & Neurobiology, Colorado State University, Fort Collins, CO 80523
Different regions of the prefrontal cortex have different functions with respect to spatial memory tasks (i.e., medial prefrontal lesions impair reference memory more than working memory, whereas lateral lesions involving insular cortex impair both). There also appear to be differences in function between the dorsal and ventral hippocampus. The purpose of this study was to determine whether the age-related changes that have been seen in the expression of the N-methyl-D-aspartate (NMDA) receptor and its subunits in horizontal sections of the prefrontal cortex and ventral hippocampus are similar throughout the prefrontal subregions and in the dorsal hippocampus. Male C57Bl/6 mice from 3 different age groups (3, 10, and 26-30 month old) were obtained from the National Institute on Aging animal colony. Receptor autoradiography was used to examine [3H]glutamate binding to the NMDA receptors. In situ hybridization was used to examine the mRNA expression of the epsilon2 subunit of the NMDA receptor. Coronal sections were obtained from one side of the brain and horizontal sections from the other with the use of a cryostat. Rostral sections through the prefrontal cortex showed a greater effect of aging on both NMDA receptor binding and epsilon2 subunit mRNA expression in lateral orbital and insular cortex than in medial subregions such as prelimbic and cingulate cortices. The more caudal areas within prefrontal subregions appeared to show more significant differences between the 3 age groups than the rostral areas. In the hippocampus, the ventral subregions showed greater age-related changes than the dorsal hippocampus. All of the ventral subregions exhibited significant declines in binding to NMDA receptors between the young and 30 month old mice, but only the upper blade of the dentate gyrus molecular layer and the stratum lacunosum/ moleculare of the CA1 region showed significant decreases in binding in the dorsal hippocampus. Significant changes during aging in the mRNA expression of the epsilon2 subunit of the NMDA receptor were only seen in the ventral hippocampus. These results demonstrated that there were regional differences in the effects of aging on the NMDA receptor both within the prefrontal cortex and the hippocampus, including a difference within prefrontal subregions between rostral and caudal areas. The greater susceptibility of the insular cortex to aging changes in NMDA receptor expression than the medial prefrontal subregions suggests that declines in both spatial reference and working memory may be due to changes within the same region. The lessor effect of aging on NMDA receptor expression in the dorsal hippocampus than the lateral prefrontal subregions suggests that age-related declines in spatial memory may be more related to prefrontal cortex changes than hippocampal.This work supported by NIH grants AG16322 to K.R.M.
Key words:
glutamate, aging, mice, memory
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