Age-related alteration of intracellular ATP maintenance in the cell suspensions of mice cerebral cortex.

Neurological alteration in the aging brain has been suggested to be due to, in part, a declined cellular energy metabolism. In order to understand age-related alteration of intracellular ATP maintenance, the present in vitro study measured change of intracellular adenosine triphosphate (ATP) content in cell suspensions of cerebral cortex isolated from male ICR mice aged 2 days (infant), 8 weeks (young adult) and 12 months (aged) under several different conditions, using the chemiluminescence technique. Among the three different ages, significant decrease of intracellular ATP content by oxygen deprivation for 15 min was observed in the cell suspensions of cerebral cortex from 12-month-old mice (P < 0.05). When cell suspensions of 8-week cerebral cortex were incubated with or without glucose (0-60 min), intracellular ATP content decreased in a time-dependent manner under both conditions, but depletion rate was significantly high in the glucose-free condition. This decrease was maximally restored by adding 1 mM glucose as tested. In addition, the ability for intracellular ATP maintenance in the presence or absence of glucose was age-dependently different. The rank order of difference of intracellular ATP content between with and without glucose was 3 months > 12 months > 2 days. The highest decrease of intracellular ATP content by incubation without glucose was observed in the 12-month samples. Sodium cyanide (100 microM) produced a gradual ATP depletion in cerebral cortex suspended from 2-day-old mice, but rapid change in both 8-week and 12-month samples. Combination of cyanide and iodoacetate (3.5 mM) rapidly depleted the intracellular ATP content in all age groups tested. These results suggest that the aging process in the cerebral cortex of mice is accompanied by alteration of maintenance of intracellular ATP homeostasis under a given condition, and this may be associated with pathological change of overall mechanisms involved in the development of neuronal disease in the senescent brain.