The hippocampus has been implicated as a crucial region in learning and memory, and damage to the hippocampus or its associated neuronal circuitry has been described in both age-related and Alzheimer's type dementia. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is thought to be critical to the fundamental functioning of the hippocampus. Recently we have developed antibodies and other molecular probes to NMDA receptor subunits which h will allow us to characterized the expression patterns of NMDA receptor subunits in both animal models of aging and Alzheimer's disease (AD) and in human post-mortem tissue from aged individuals and those with AD. In addition we will examine the role of transcriptional regulation of the NMDA receptor subunits as it relates to any differences seen in expression. In order to examine the importance of any changes which are found, we will examine the patterns of expression of NMDA receptor subunits in treatment paradigms which have been shown to ameliorate behavioral aspects of age-related and Alzheimer's type dementia. An understanding of the role of NMDA receptor in the pathogenesis of age-related and Alzheimer's type dementia could further our understanding of the underlying pathology of these disorders and may suggest new therapeutic approaches.
