Short-term mental activation accelerates the age-related decline of high-energy phosphates in rat cerebral cortex

Abstract

Aging in rats is associated with a significant decline in brain levels of energy-rich phosphates, including ATP and creatine phosphate. To test the effects of transient mental activity mediated by psychometric testing, and of metabolic inhibition of pyruvate dehydrogenase (PDH) (an enzyme complex that generates acetyl coenzyme A (CoA) to feed the mitochondrial tricarboxylic acid cycle), we compared adult (52 to 64-week-old) and aged (104-week-old) rats with and without intracerebral injections of the PDH inhibitor, bromopyruvate (BP), in the presence and in the absence of extensive psychometric testing by standard passive avoidance and hole board test paradigms. As compared with mental rest, short-term mental activation was associated with higher levels of energy-rich phosphates in the cerebral cortex of both adult and aged animals, but did not prevent the age-dependent decline in these phosphates. ATP turnover was markedly increased by mental activity, but was less pronounced in aged animals. In the hippocampus, less marked changes in the energy pool became obvious. The abnormalities in energy metabolism indicate an age-dependent and stress-accentuated reduction of the capacity to meet such energy-dependent demands as mixed function oxidation in the aged brain. BP did not change brain levels of energy-rich phosphates, indicating that the damage caused by decreased PDH activity can be compensated for both in adult and in aged animals.