For example, both the hypothalamus and anterior pituitary express GCRs to provide negative feedback loops within the HPA axis by suppressing CRH and ACTH production ( Godoy et al., 2018).įigure 1. Glucocorticoid receptors (GCR) are expressed in most tissues in mammals, however, and the physiological processes affected are wide-ranging. The autonomic component of the stress response, which includes vasoconstriction, inducing perspiration, and suppressing digestive activity, works in conjunction with glucocorticoids to provide an acute adaptation to stressful stimuli. They also suppress the inflammatory actions of the immune system and, thus, synthetic glucocorticoids are commonly prescribed in humans as anti-inflammatory medications. Glucocorticoids comprise the main downstream component of the neuroendocrine response to stress and primarily serve to stimulate gluconeogenesis in the liver and lipolysis for energy production. Upon stimulation by CRH, the anterior pituitary releases adrenocorticotropin-releasing hormone (ACTH), which then induces adrenal gland secretion of glucocorticoids into the bloodstream. Signaling along this pathway begins with the release of corticotropin-releasing hormone (CRH) by neurosecretory cells in the paraventricular nucleus of the hypothalamus. The brain plays a key role in the response to stress, which includes higher order processing of stress-related information and an immediate physiological response executed by the hypothalamus, the proverbial “fight or flight response.” In addition to direct autonomic input to specific tissues, the stress response involves sending hormonal signals throughout the body via the hypothalamic-pituitary-adrenal (HPA) axis (depicted in Figure 1). The impact of stress on human health has been extensively investigated and the role of stress in disease pathology has become apparent over recent decades ( Chrousos, 2009). In this review, we will discuss the effects of stress on the brain, with a focus on glucocorticoid action in the hippocampus and cerebral cortex, and emerging evidence of an ability of selenium to normalize neurological function in the context of various stress and glucocorticoid exposure paradigms in rodent models. In recent years, the protective role of the antioxidant micronutrient selenium against the negative impact of externally applied stress has begun to come to light. Intense acute or chronic elevation of glucocorticoids, a class of stress hormone, can have deleterious neurological effects, however, including memory impairments and emotional disturbances. The stress response is an important tool in an organism’s ability to properly respond to adverse environmental conditions in order to survive. Pacific Biosciences Research Center, School of Ocean and Earth Science and Technology, University of Hawaii at Manoa, Honolulu, HI, United States.

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