In order to test the hypothesis that neurotransmitter synthesis in the brains of aged animals is even more sensitive to hypoxia than in the brains of younger animals, the synthesis of acetylcholine and other neurotransmitters derived from glucose (glutamate, aspartate, and gamma-aminobutyrate) will be studied with varying levels of chemical and hypoxic hypoxia in the brains of young, mature and aged mice and rats. The synthesis of acetylcholine and the other neurotransmitters will be studied with (U-14C)glucose by methods developed by the PI. Synthesis will be determined in young, mature and aged mice during chemical hypoxia induced by injection of KCN or NaNO2 as in the PI's previous work. Synthesis will be determined in young, mature and aged rats during hypoxic hypoxia in animal preparations well standardized in the Department of Neurology at N.Y. Hospital at Cornell. These experiments will determine whether neurotransmitter synthesis in aged brains is more sensitive to hypoxia than in younger brains and whether the turnover of these neurotransmitters varies with age.
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