Aging of the hypothalamic-pituitary-adrenal axis in nonhuman primates with depression-like and aggressive behavior.

We have investigated aging of the hypothalamic-pituitary-adrenal (HPA) axis in female rhesus monkeys that differ in adaptive behavior. Plasma cortisol (F) and dehydroepiandrosterone sulfate (DHEA-S) concentrations under basal conditions and under acute psycho-emotional stress were evaluated in blood plasma of young (6-8 years) and old (20-27 years) female rhesus monkeys with various types of adaptive behavior (aggressive, depression-like, and average). We have found that the age-related changes in the HPA axis of monkeys with depression-like behavior were accompanied by the maximal absolute and relative hypercortisolemia under both basal conditions and stress. Moreover, young aggressive monkeys, in comparison with young monkeys of other behavior groups, demonstrated the highest plasma levels of DHEA-S and the lowest molar ratios between F and DHEA-S. Thus, age-related dysfunctions of the HPA axis are associated with adaptive behavior of animals.

Circadian and age-related changes in stress responsiveness of the adrenal cortex and erythrocyte antioxidant enzymes in female rhesus monkeys.

BACKGROUND: The objective of this study was to evaluate the role of the adrenal cortex in the regulation of antioxidant enzyme defense and to characterize this regulation in different age periods. METHODS: Five young and five old female rhesus monkeys were subjected to 2 hours squeeze cage restraint stress at 0900 or 1500 hours. Plasma levels of corticosteroids and activities of erythrocyte antioxidant enzymes were measured before the stress and 30, 60, 120, 240 minutes after beginning of the stress. RESULTS: Young monkeys showed a circadian rhythm in stress responsiveness as measured by corticosteroids and glutathione reductase. The rhythm was attenuated in old animals. Age-related changes in the overall level of response to the afternoon stress were also seen in the corticosteroid and glutathione reductase measures. CONCLUSIONS: The study demonstrated that corticosteroids play an essential role in the regulation of antioxidant enzyme defense in stress conditions and that the reliability of their regulation decreases with age.