Corticosteroids and the brain

Abstract

The brain is continuously exposed to varying levels of adrenal corticosteroid hormones such as corticosterone in rodents and cortisol in humans. Natural fluctuations occur due to ultradian and circadian variations or are caused by exposure to stressful situations. Brain cells express two types of corticosteroid receptors, i.e. mineralocorticoid and glucocorticoid receptors, which differ in distribution and affinity. These receptors can mediate both rapid non-genomic and slow gene-mediated neuronal actions. As a consequence of these factors, natural (e.g. stress-induced) shifts in corticosteroid level are associated with a complex mosaic of time- and region-dependent changes in neuronal activity. A series of experiments in humans and rodents have revealed that these time- and region-dependent cellular characteristics are also reflected in distinct cognitive patterns after stress. Thus, directly after a peak of corticosteroids, attention and vigilance are increased, and areas involved in emotional responses and simple behavioral strategies show enhanced activity. In the aftermath of stress, areas involved in higher cognitive functions become activated allowing individuals to link stressful events to the specific context and to store information for future use. Both phases of the brain's response to stress are important to face a continuously changing environment, promoting adaptation at the short as well as long term. We argue that a balanced response during the two phases is essential for resilience. This balance may become compromised after repeated stress exposure, particularly in genetically vulnerable individuals and aggravate disease manifestation. This not only applies to psychiatric disorders but also to neurological diseases such as epilepsy.

The effects of different rearing conditions on sexual maturation and maternal care in heterozygous mineralocorticoid receptor knockout mice

“…The MR is a high affinity receptor for cortisol (in humans) and corticosterone (in rodents) that is predominantly expressed in limbic-cortical areas such as the hippocampus, amygdala and medial prefrontal cortex; areas that additionally express the lower-affinity glucocorticoid receptor (GR) (Joëls, 2018;Reul and Kloet, 1985). MR and GR interact to mediate an adaptive response to stress; an imbalance between the two is hypothesized to increase the risk of developing psychopathology (Harris et al, 2013;Joëls, 2018). In humans, MR haplotypes have been shown to sex-specifically moderate the effects of childhood maltreatment on (sub-clinical signs of) depression (Vinkers et al, 2015).…”

Human defensive freezing is associated with acute threat coping, long term hair cortisol levels and trait anxiety

“…GCs in turn facilitate energy mobilization, recovery and normalization to homeostasis, as well as adaptation of physiological responses to future threat (De Kloet, Joëls, & Holsboer, 2005;Joels, 2017;Oitzl, Champagne, van der Veen, & de Kloet, 2010). Studies in rats and primates demonstrated the involvement of the HPA-axis in freezing reactions by showing a positive association between threat-induced freezing and increased basal cortisol levels in anxious animals (De Boer, Slangen, & Van der Gugten, 1990;Dettmer, Novak, Suomi, & Meyer, 2012;Kalin et al, 1998;Núñez, Ferré, Escorihuela, Tobeña, & Fernández-Teruel, 1996).…”

Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease

“…Finally, estrone can be converted into estradiol by 17β-HSD [45], whilst testosterone can be converted by 5α-reductase into 5α-dihydrotestosterone (DHT) and then by 3α-HSD into androstanediol [49]. Although not discussed in this review, for information on corticosteroids ( Figure 2) and their role in the brain there are recent detailed commentaries [50,51].…”