Age-related changes in cerebral oxidative metabolism. Implications for drug therapy.
Glucose metabolism in the brain is of central significance. It contributes to the synthesis of the neurotransmitters acetylcholine, glutamate, aspartate, gamma-aminobutyric acid (GABA) and glycine, and yields adenosine triphosphate (ATP) as the driving force of almost all cellular and molecular work. Neuronal glucose metabolism is controlled antagonistically by insulin and cortisol via amplification and desensitisation of the insulin signal from the insulin receptor. Normal aging of mammalian brains is associated with numerous inherent metabolic changes. The metabolic changes that are of pivotal importance include probable primary inherent variations in the neuronal insulin receptor, the desensitisation of the neuronal insulin receptor by circulating cortisol and receptor dysfunction subsequent to changes in membrane structure and function. As a consequence, slight aberrations in glucose/energy metabolism become obvious under resting conditions, indicating incipient variations of neuronal homeostasis as a common path in the aging process. Subsequent to the changes in glucose metabolism and energy production, variations occur in acetylcholine synthesis and release, extracellular concentration and receptor binding of glutamate and cytosolic Ca++ homeostasis. Additionally, free radical formation and membrane structure changes must be considered as primary changes during aging. Stressful events occurring more frequently during aging aggravate and prolong these changes that are accompanied by membrane liability.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoyer
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S
Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Germany.
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004358:Drug Therapy / Q000379:methods; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*
D005947:Glucose; D010100:Oxygen