This review is devoted to the phenomenon of intermittent hypoxic training and is aimed at drawing the attention of researchers to the necessity of studying the mechanisms mediating the positive, particularly neuroprotective, effects of hypoxic training at the molecular level. The review briefly describes the historical aspects of studying the beneficial effects of mild hypoxia, as well as the use of hypoxic training in medicine and sports. The physiological mechanisms of hypoxic adaptation, models of hypoxic training and their effectiveness are summarized, giving examples of their beneficial effects in various organs including the brain. The review emphasizes a high, far from being realized at present, potential of hypoxic training in preventive and clinical medicine especially in the area of neurodegeneration and age-related cognitive decline.
Objective. The aim of the study was to reveal the role of HIF-1 in the effects of hypoxic postconditioning in the rat experimental model of depression "learned helplessness".
Materials and methods. The studies were performed in the "learned helplessness" paradigm which represents a reliable experimental model of depression in rats. The development of the pathology was evaluated in the behavioral open field test and by the baseline level of plasma corticosterone. Correction of behavioral deficit was performed by three episodes of hypoxic postconditioning (360 mmHg, 2 h). Changes in the immunopositivity of HIF-1 and erythropoietin in the hippocampus of rats were evaluated. An inhibitor of HIF-1 subunit translation topotecan (1 mg/kg, i.p., Santa Cruz, USA) was used on the 4th day after the footshock stress. On the 9th day, animals were tested in the open field test to assess the level of depressive-like behavior.
Results. It was shown that postconditioning by three episodes of mild hypobaric hypoxia resulted in the correction of behavioral deficit produced by the "learned helplessness aversive stress, and the levels of corticosterone did not differ from the baseline in these animals. These behavioral and hormonal effects were accompanied by the increased level of immunopositive HIF-1 and its transcriptional downstream target erythropoietin in the dorsal and ventral hippocampus. Using of HIF-1 inhibitor topotecan dramatically worsen the severity of the depressive-like symptoms.
Conclusion. The findings suggest that HIF-1 appears to have the antidepressant-like activities and that hypoxic postconditioning-induced stimulation of HIF-1 and erythropoietin level might contribute to the endogenous mechanisms which compensate for the pathogenic effects of stressors, particularly for the development of stress-induced depression.
Comparative analysis of available literature data on the pathogenetic neuroendocrine mechanisms of depression and post-traumatic stress disorder (PTSD) is provided in this review to identify their common features and differences. We discuss the multidirectional modifications of the activity of cortical and subcortical structures of the brain, levels of neurotransmitters and their receptors, and functions of the hypothalamic-pituitary-adrenocortical axis in depression and PTSD. The analysis shows that these disorders are examples of opposite failures in the system of adaptive stress response of the body to stressful psychotraumatic events. On this basis, it is concluded that the currently widespread use of similar approaches to treat these disorders is not justified, despite the significant similarity of their anxiety-depressive symptoms; development of differential therapeutic strategies is required.
In the rat experimental model of posttraumatic stress disorder (PTSD), the level of blood corticosterone was at least eight-fold increased (an overrelease). The use of hypobaric hypoxic preconditioning or short-term inhibition of glucocorticoid synthesis by metyrapone injection prevented development of the experimental PTSD.
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