https://sites.oxy.edu/clint/physio/article/neurobiologyofdepression.pdf

Neurobiology of depression.

In this review, we have described the function of MR and GR in hippocampal neurons. The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals. The following specific inferences can be made on the basis of the currently available facts. 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain. MRs are close to saturated with low basal concentrations of corticosterone, while high corticosterone concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and conditional. The action depends on cellular context, which is in part determined by other signals that can activate their own transcription factors interacting with MR and GR. These interactions provide an impressive diversity and complexity to corticosteroid modulation of gene expression. 3. Conditions of predominant MR activation, i.e., at the circadian trough at rest, are associated with the maintenance of excitability so that steady excitatory inputs to the hippocampal CA1 area result in considerable excitatory hippocampal output. By contrast, additional GR activation, e.g., after acute stress, generally depresses the CA1 hippocampal output. A similar effect is seen after adrenalectomy, indicating a U-shaped dose-response dependency of these cellular responses after the exposure to corticosterone. 4. Corticosterone through GR blocks the stress-induced HPA activation in hypothalamic CRH neurons and modulates the activity of the excitatory and inhibitory neural inputs to these neurons. Limbic (e.g., hippocampal) MRs mediate the effect of corticosterone on the maintenance of basal HPA activity and are of relevance for the sensitivity or threshold of the central stress response system. How this control occurs is not known, but it probably involves a steady excitatory hippocampal output, which regulates a GABA-ergic inhibitory tone on PVN neurons. Colocalized hippocampal GRs mediate a counteracting (i.e., disinhibitory) influence. Through GRs in ascending aminergic pathways, corticosterone potentiates the effect of stressors and arousal on HPA activation. The functional interaction between these corticosteroid-responsive inputs at the level of the PVN is probably the key to understanding HPA dysregulation associated with stress-related brain disorders. 5. Fine-tuning of HPA regulation occurs through MR- and GR-mediated effects on the processing of information in higher brain structures. Under healthy conditions, hippocampal MRs are involved in processes underlying integration of sensory information, interpretation of environmental information, and execution of appropriate behavioral reactions. Activation of hippocampal GRs facilitates storage of information and promotes elimination of inadequate behavioral responses. These behavioral effects mediated by MR and GR are linked, but how they influence endocrine regulation is not well understood. 6. Dexamethasone preferentially targets the pituitary in the blockade of stress-induced HPA activation. The brain penetration of this synthetic glucocorticoid is hampered by the mdr1a P-glycoprotein in the blood-brain barrier. Administration of moderate amounts of dexamethasone partially depletes the brain of corticosterone, and this has destabilizing consequences for excitability and information processing. 7. The set points of HPA regulation and MR/GR balance are genetically programmed, but can be reset by early life experiences involving mother-infant interaction. 8. (ABSTRACT TRUNCATED)

/pdf/brain-corticosteroid-receptor-balance-in-health-and-disease-1s4dl9ggav.pdf

Brain corticosteroid receptor balance in health and disease.

Physiological changes in fish from stress in aquaculture with emphasis on the response and effects of corticosteroids

Stress is a part of every life to varying degrees, but individuals differ in their stress vulnerability. Stress is usefully viewed from a biological perspective; accordingly, it involves activation of neurobiological systems that preserve viability through change or allostasis. Although they are necessary for survival, frequent neurobiological stress responses increase the risk of physical and mental health problems, perhaps particularly when experienced during periods of rapid brain development. Recently, advances in noninvasive measurement techniques have resulted in a burgeoning of human developmental stress research. Here we review the anatomy and physiology of stress responding, discuss the relevant animal literature, and briefly outline what is currently known about the psychobiology of stress in human development, the critical role of social regulation of stress neurobiology, and the importance of individual differences as a lens through which to approach questions about stress experiences during development and child outcomes.

https://sites.oxy.edu/clint/physio/article/neurobiologyofstressanddevelopment.pdf

The neurobiology of stress and development.

Animals respond to stress by activating a wide array of behavioral and physiological responses that are collectively referred to as the stress response. Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by glucocorticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorticoid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from limbic, mid-brain, and brain stem nuclei. The stress response is also mediated in part by brain stem noradrenergic neurons, sympathetic andrenornedullary circuits, and parasympathetic systems. In summary, the aim of this review is to discuss the role of the HPA axis in the integration of adaptive responses to stress. We also identify and briefly describe the major neuronal and endocrine systems that contribute to the regulation of the HPA axis and the maintenance of homeostasis in the face of aversive stimuli.

The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress.

LOCALISATION OF 11β-HYDROXYSTEROID DEHYDROGENASE—TISSUE SPECIFIC PROTECTOR OF THE MINERALOCORTICOID RECEPTOR

Administrations of the glucocorticoid receptor antagonist (anti-glucocorticoid, RU38486) and the mineralocorticoid antagonist (anti-mineralocorticoid, RU28318) followed by frequent, sequential blood s

On the role of brain mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulation.

Publisher Summary This chapter provides an overview of the current understanding of the dynamics of the hypothalamuspituitary-adrenal (HPA) system in the adult rat The chapter particularly emphasizes on the role of glucocorticoid receptors in this process In the adult organism, glucocorticoids (GCs) serve a wide variety of regulatory and permissive functions, aimed basically at controlling the organism's responses to stress, and at regulating circadian-driven activities The principal GC synthesized by the rat adrenal cortex is corticosterone (CORT) CORT levels display a pronounced circadian rhythmicity: they are highest immediately preceding the animal's active period, and lowest at the end of this period During development, however, GCs have also been shown to produce, in experimental animals, permanent effects on growth and differentiation of a number of systems, including the central nervous system In rats, for example, high doses of GCs administered neonatally cause a decrease in mitosis and myelination, as well as altered neural morphogenesis In addition, the chapter also reviews some of the relevant human literature and considers the implications of animal studies for the field of human functional teratology

Stress, glucocorticoids and development

Ontogeny of type I and type II corticosteroid receptors in the rat hippocampus.

In vitro cytosolic receptor binding assays and autoradiographical procedures have shown the localization and properties of two corticoid receptor types in the brain of the rat, a species in which corticosterone (B) is the predominant circulating glucocorticoid. The present study was designed to examine the localization, heterogeneity, and binding specificity of corticosteroid receptors in the brain of the hamster, a species which secretes B and cortisol (F), the latter being the predominantly circulating form. Our results show that two corticoid receptor systems can also be distinguished in the hamster brain. The type I receptor has an almost exclusive localization in the hippocampal region and the amounts measured in hypothalamic or whole brain (without the hippocampus) were negligible. The type II receptor, on the other hand, has a wider distribution in the brain. Scatchard and Woolf analyses of the binding data revealed that the hamster type I receptor has similar affinity to both F and B [dissociation...

W. Sutanto

Papers

LOCALISATION OF 11β-HYDROXYSTEROID DEHYDROGENASE—TISSUE SPECIFIC PROTECTOR OF THE MINERALOCORTICOID RECEPTOR

On the role of brain mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulation.

Stress, glucocorticoids and development

Ontogeny of type I and type II corticosteroid receptors in the rat hippocampus.

Species-specificity of corticosteroid receptors in hamster and rat brains.