The experiments proposed will examine the expression, distribution, and glycosylation of neuronal nicotinic acetylcholine receptors and glutamate receptors in the mammalian nervous system. Transfection of cDNAs encoding glutamate receptors into cultured cells will be used to explore the relationship between receptor subunit composition and the sensitivity of the cell to kainic acid induced excitotoxicity. The working hypothesis is that neurodegenerative disease that are often associated with diseases of aging such as senile dementia can result from the altered subunit expression, receptor assembly, or subneuronal localization of glutamate or nicotinic acetylcholine receptors. The consequence of expressing receptors that are functionally altered or that are not within their normal context of expression could render neurons essentially nonfunctional, or susceptible to damage and possibly death. To begin the test of this hypothesis, antisera to subunits that compose these receptors have been prepared and will be used to localize these subunits, determine the associations between the subunits, and measure the glycosylation of each subunit in the brains of rats. Upon determining the association between glutamate receptor subunits and their location in vivo, the corresponding cDNAs will be transfected into cultured cells, and the influence that receptors of various subunit composition has on imparting to the transfected cell sensitivity to agonist induced excitotoxic death will be determined.
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