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.
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.
Clinical and experimental data point to existence of disturbances of adaptive ability of aged organism to extreme impacts. However mechanisms of these disturbances are not clear yet. The purpose of the investigation was to study age-related changes in reaction of erythrocyte antioxidant enzyme system in response to acute psycho-emotional stress and a possible role of these changes in age-related alterations of oxygen blood transport in nonhuman primates. Ten young (6-8 years) and ten old (20-26 years) healthy female rhesus monkeys were subjected to acute moderate psychoemotional stress (two hours squeeze cage restraint) at 1500h. Plasma cortisol, lipid peroxidation products (TBARS) and activities of superoxide dismutase (SOD), glutathione peroxidase, gluthatione reductase (GR), and gluthatione-Stransferase in erythrocytes were measured before stress and at 30, 60, 120, 240 min and 24 hours after beginning of the stress. We have found for the first time that SOD activity decreased in response to the stress in young monkeys while it increased in the half of old monkeys. Young animals also demonstrated essentially higher increase in GR activity and plasma cortisol level in response to the restraint in comparison with old monkeys. Level of TBARS did not practically change in response to the stress in young animals and significantly increased in old monkeys. The study demonstrated that the age-related alterations in SOD and GR stress responsiveness lead to activation of peroxide oxidation of lipids that may be considered as an important factor of aging damage of erythrocyte functioning and reliability of oxygen transport to tissues under stress conditions.
Experimental study was carried out on young mature (6-8 years) and old (21-27 years) rhesus macaques with anxious and depression-like behavior and with standard (control) adaptive behavior. The responce of the adenohypophysis to arginine vasopressin depended on age and the type of adaptive behavior. Young animals with standard behavior demonstrated much higher concentrations of ACTH in the peripheral plasma in response to arginine vasopressin than old animals. The secretion of ACTH was higher in young and old animals with anxious and depressive-like adaptive behavior and they exhibited no age-specific differences in reaction to arginine vasopressin, which were observed in control animals. Preinjection of vasopressin V1b receptor antagonist to a female with high anxiety sharply reduced ACTH secretion in response to insulin-induced hypoglycemia in comparison with ACTH secretion under the same conditions without antagonist injection. These results suggested that the vasopressinergic system of animals with anxious and depressive behavior plays an important role in the regulation of ACTH secretion and in activity of the hypothalamic-pituitary-adrenal system in general.
We have investigated age-related changes in the reliability of glutathione-related antioxidant enzyme defense in monkeys that differ in adaptive behavior. Activities of gluthatione reductase (GR), glutathione peroxidase (GSH-Px), and gluthatione-S-transferase (GST) and also lipid peroxidation products (TBARS) under basal conditions and under acute psycho-emotional stress were evaluated in erythrocytes of young (6-8 years) and old (20-27 years) female rhesus monkeys with depression-like and standard (control) behavior. We have found that young animals with depression-like behavior, in comparison with young monkeys of standard behavior, demonstrated higher activity of GR in basal conditions and no significant changes in response to acute immobilization stress. With aging the activity of GR increased in monkeys with standard behavior in basal conditions but retained the ability to increase under acute stress. At the same time during aging in monkeys with depression-like behavior GR activity did not undergo significant changes in basal conditions and did not change in response to acute stress. Moreover, old animals with depression-like behavior demonstrated reduced activity of GSH-Px. More pronounced disturbances in GR and GSH-Px activities in animals with depression-like behavior evidence a more marked decrease in the reliability of antioxidant enzyme defense of cells and lead to activation of lipid peroxidation that may be considered as an important factor of aging. Thus, age-related dysfunctions of the antioxidant enzyme system correlate with the type of adaptive behavior characteristic of animals.
Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.
Activity of glutathione-dependent antioxidant enzymes (glutathione peroxidase, glutathione reductase, and glutathione transferase) in blood erythrocytes from female Macaca mulatta (6-8 and 20-26 years) was measured during activation of the hypothalamic-pituitary-adrenal system under conditions of acute psychoemotional stress (2-h restraint stress). Glutathione reductase activity increased during stress, depended on the time of day, and strongly correlated with blood corticosteroid level. Circadian variations in stress reactivity of glutathione reductase during aging were accompanied by similar changes in stress reactivity of the hypothalamic-pituitary-adrenal system.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.