title: Age-related alterations in energy metabolism contribute to the increased vulnerability of the aging brain to anoxic damage.
abstract: Aging increases the vulnerability of brain tissue to anoxia and ischemia. We investigated whether age-related alterations in energy metabolism underlie this increased vulnerability. Energy metabolism was manipulated in hippocampal slices from Fischer 344 rats of ages 6-9 (young adult), 16-19 (middle-aged adult), and 26-29 (aged adult) months by altering glucose concentrations or by using lactate instead of glucose as the metabolic substrate. Extracellular K+ activity (K+o) and synaptic excitability were monitored in stratum pyramidale of hippocampal subfield CA1. Aging diminished how well increasing concentrations of glucose delayed onset of anoxic depolarization and improved postanoxic recovery of K+o homeostasis and synaptic transmission. Hippocampal slices from all age groups responded to anoxia similarly when lactate was present instead of glucose. Also, no age-related differences were seen in normoxic ATP and phosphocreatine levels. These results suggest that an age-related decline in the glycolytic capacity of brain cells contributes to earlier onset of anoxic depolarization and poorer recovery of ion homeostasis and synaptic transmission in aging brain tissue.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, FL 33136, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Roberts
authors.forename: C P
authors.initials: CP
authors.lastname: Chih
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D011188:Potassium