Age and insulin-like growth factor-1 modulate N-methyl-D-aspartate receptor subtype expression in rats

N-Methyl-D-aspartate (NMDA) receptors have been reported to have an importa nt role in synaptic plasticity and neurodegeneration, Two major subtypes of these receptors, NMDAR1 and NMDAR2, are present in brain and heterogeneity of these receptors have been reported to define specific functional respon ses, In this study, the effects of age and chronic insulin-like growth fact or-1 (IGF-1) administration on NMDA receptor density and subtype expression were investigated in frontal cortex, CA1, CA2/3 and the dentate gyrus of t he hippocampus of young (10 months), middle-aged (21 months) and old (30 mo nths) male Fisher 344xBrown Norway (F1) rats. No age-related changes in I-1 25-MK-801 binding or NMDAR1 protein expression were observed in hippocampus or frontal cortex. However, analysis of NMDAR2A and NMDAR2B protein expres sion in hippocampus indicated a significant decrease between 21 and 30 mont hs of age and administration of IGF-1 increased these receptor subtypes, In cortex, NMDAR2A and NMDAR2B protein expression were not influenced by age or IGF-1 treatment, although NMDAR2C protein expression decreased with age and this decline was not ameliorated by IGF-1 administration, These data de monstrate that NMDA receptor subtypes are altered with age in a regional an d subtype specific manner, We conclude that both age and IGF-1 regulate the expression of NMDA receptor subtypes and suggest that age-related changes in NMDA receptor heterogeneity may result in functional changes in the rece ptor that have relevance for aging. (C) 2000 Elsevier Science Inc.