Preconditioning by Moderate Hypoxia Increases the Amount of Corticosteroid Receptors in the Rat Brain in a Model of Depression

Abstract

Abstract—The involvement of corticosteroid brain receptors in the antidepressant-like effects of moderate hypobaric hypoxia was studied in a rat model of depression (the learned helplessness paradigm) using immunohistochemistry. The formation of a depressive-like state is accompanied by a significant deficiency in glucocorticoid receptors in the brain which is most pronounced in the dentate gyrus of the hippocampus, as well as by a considerable shift in the relative balance between gluco- and mineralocorticoid receptors towards the latter. The use of hypoxic preconditioning prior to stress exposure in the learned helplessness paradigm prevented the development of depression and eliminated receptor deficiency by post-stress day 10 in the hypothalamus and during the first day of the observation in the neocortex. In the hippocampus of preconditioned animals, stress adaptation was accompanied by an acute and consistent increase in glucocorticoid receptor immunoreactivity, with a relative balance of the two receptor types in the CA1 field, and considerable glucocorticoid receptor prevalence in the dentate gyrus. It may be assumed that deficiency and imbalance of hippocampal corticosteroid receptors is one of the most important molecular mechanisms of glucocorticoid regulation dysfunction in stress-induced psychopathologies, whereas the post-stress activation of receptor expression contributes to the manifestation of the antidepressant-like effects of moderate hypoxia. The data obtained expand the current views on the endocrine mechanisms of the formation and prevention of depressive disorders and increase the translation potential of moderate hypoxia as a drug-free strategy for their treatment.