EFFECT OF ACUTE STRESS ON HIPPOCAMPAL GLUTAMATE LEVELS AND SPECTRIN PROTEOLYSIS IN YOUNG AND AGED RATS

Aging in rats is associated with a loss of hippocampal neurons, which may contribute to age-related cognitive deficits. Several lines of evi dence suggest that stress and glucocorticoids may contribute to age-re lated declines in hippocampal neuronal number. Excitatory amino acids (EAAs) have been implicated in the glucocorticoid endangerment and str ess-induced morphological changes of hippocampal neurons of young rats . Previously, we have reported that acute immobilization stress can in crease extracellular concentrations of the endogenous excitatory amino acid, glutamate, in the hippocampus. The present study examined the e ffect of an acute bout of immobilization stress on glutamate levels in the hippocampus and medial prefrontal cortex of young (34-month) and aged (22-24-month) Fischer 344 rats. In addition, the effect of stress on spectrin proteolysis in these two brain regions was also examined. Spectrin is a cytoskeleton protein that contributes to neuronal integ rity and proteolysis of this protein has been proposed as an important component of EAA-induced neuronal death. There was no difference in b asal glutamate levels between young and old rats in the hippocampus or medial prefrontal cortex. During the period of restraint stress a mod est increase in glutamate levels in the hippocampus of young and aged rats was observed. After the termination of the stress procedure, hipp ocampal glutamate concentrations continued to rise in the aged rats, r eaching a level approximately five times higher than the young rats, a nd remained elevated for at least 2 h after the termination of the str ess. A similar pattern was also observed in the medial prefrontal cort ex with an augmented poststress-induced glutamate response observed in the aged rats. There was no increase in spectrin proteolysis in the h ippocampus or medial prefrontal cortex of young or aged rats after str ess or under basal nonstress conditions. The enhanced poststress gluta mate response in the aged rats may contribute to the increased sensiti vity of aged rats to neurotoxic insults.