GLUTAMATE RECEPTOR PROCESSING IN AGING

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Among the many receptor types implicated in age-related alterations of normal neurotransmission are the fast excitatory glutamate-activated cationic channel receptors (GLuR). Since these receptors are thought to play a central role in establishing and maintaining optimal cognitive function, and the aberrant expression or regulation of these receptors has been implicated in neuronal damage, understanding the mechanisms that regulate their expression is central to determining how these receptors may participate in age-related changes in the brain. One way GluR function can be regulated is through alternative splicing and RNA editing of subunit transcript. This imparts significantly differently functional properties upon the mature receptor. In this one-year R03 proposal, I will examine GluR subunit RNA editing and/or splicing from various brain regions of young, adult and aged mice to test the following hypothesis. Specific Aim 1. Alternative Splicing of Glutamate Receptor Subunits in the Aging Brain. The hypothesis to be tested is: The relative of alternatively spliced transcripts of GluR1, GluR2, GluR3, GluR4 is altered in the aged mouse brain relative to young or adult mice. Specific Aim 2. RNA editing of Non-NMDA Glutamate Receptor Subunits in the Aging Brain. The hypothesis to be tested is: The relative ratio of edited versus non-edited GluR2, GluR5, or GluR6 is altered in the aged mouse brain relative to young or adult mice.