Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia

Abstract

Adaptation of organisms to stressors is coordinated by the hypothalamic-pituitary-adrenal axis (HPA), which involves glucocorticoids (GCs) and glucocorticoid receptors (GRs). Although the effects of GCs are well characterized, their impact on brain adaptation to hypoxia/ischemia is still understudied. The brain is not only the most susceptible to hypoxic injury, but also vulnerable to GC-induced damage, which makes studying the mechanisms of brain hypoxic tolerance and resistance to stress-related elevation of GCs of great importance. Cross-talk between the molecular mechanisms activated in neuronal cells by hypoxia and GCs provides a platform for developing the most effective and safe means for prevention and treatment of hypoxia-induced brain damage, including hypoxic pre- and post-conditioning. Taking into account that hypoxia- and GC-induced reprogramming significantly affects the development of organisms during embryogenesis, studies of the effects of prenatal and neonatal hypoxia on health in later life are of particular interest. This mini review discusses the accumulated data on the dynamics of the HPA activation in injurious and non-injurious hypoxia, the role of the brain GRs in these processes, interaction of GCs and hypoxia-inducible factor HIF-1, as well as cross-talk between GC and hypoxic signaling. It also identifies underdeveloped areas and suggests directions for further prospective studies.

Short-Term Mild Hypoxia Modulates Na,K-ATPase to Maintain Membrane Electrogenesis in Rat Skeletal Muscle

“…Thus, in contrast to prolonged (3 days) experimental hypoxia, which increased the release of endogenous ouabain [ 42 ], short-term (3 h) exposure to HH decreases serum ouabain level. Serum corticosterone, which is often used as a biomarker of stress and cross-talked with hypoxic signaling [ 43 ], has not changed significantly ( Figure 1 e).…”

Fear Stress During Pregnancy Affects Placental m6A-Modifying Enzyme Expression and Epigenetic Modification Levels

“…The hypothalamic–pituitary–adrenal (HPA) axis has been the focus of most studies on the relationship between stress and fetal stunting. It is hypothesized that pregnancy stress can overactivate maternal HPA axis function, thereby resulting in increased glucocorticoid (GC) levels ( Howland et al, 2017 ; Anifantaki et al, 2021 ; Rybnikova and Nalivaeva, 2021 ). Maternal GC overexpression causes alterations in intrauterine HPA axis programming in the offspring, thereby affecting the development and health of the offspring ( Howland et al, 2017 ).…”

Changes in Hippocampus and Amygdala Volume with Hypoxic Stress Related to Cardiorespiratory Fitness under a High-Altitude Environment

“…Activation of the hypothalamic-pituitary-adrenal axis (HPA) is a hallmark of the stress response [7]. At the level of the organism, a hypoxic challenge is perceived as a non-specific stress, and hypoxia could upregulate the setpoint of the HPA axis and augment adrenal steroidogenic production, resulting in neuroinflammation and neuronal cell death [8]. Highaltitude hypoxia stress affects a wide range of brain areas [4,9].…”

“…Highaltitude hypoxia stress affects a wide range of brain areas [4,9]. Major brain regions with 2 of 13 structural and functional abnormalities are particularly vulnerable to hypoxic stress, including the amygdala and hippocampus [8]. Changes in the amygdala and hippocampus under high-altitude hypoxia stress may be due to the influence of inflammation [10,11].…”