Glucocorticoid programming of neuroimmune function

Abstract

Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases.

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

“…These receptors belong to the superfamily of nuclear receptors and act as ligand‐activated transcription factors, regulating gene expression by binding to specific DNA‐responsive elements. Although the regulation by HPGC of the genes here evaluated has not yet been described, it is already known that the expression of ATF3, c‐fos, GFAP, Iba1, IL‐1β and TNFα can be regulated by PR‐ and/or GR‐dependent mechanisms, thus enabling their regulation by the steroid.…”

Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail.

“…However, the postnatal period represents a more critical period for HPA axis maturation in most mammals and some bird species (Kapoor et al, 2006;Sims and Holberton, 2000;Wada et al, 2009), when both CORT and cortisol are present in equal amounts (Jenkins and Porter, 2004). As the effects of developmental stress can vary depending on the duration of early stress exposure, more work is required to establish any vulnerable windows of sensitivity to prenatal elevations in glucocorticoids (Walker and Spencer, 2018).…”

“…Alternatively, (2) prenatal CORT may prolong the immediate immunosuppressive state typically observed in animals exposed to stress in the short term (Dimatelis et al, 2012;Wei et al, 2012). The importance of this is that developmental stress may program different neuroimmune responses depending on the developmental stage at which an individual is exposed to stress, the type of stressor experienced and the quality of the environment to which the individual is exposed in later life (Walker and Spencer, 2018). Such effects may be adaptive or transmitted through generations (Ericsson et al, 2016;Grindstaff et al, 2006).…”

“…Cytokines can potently activate the HPA axis and induce glucocorticoid secretion during an immune or stress response (Felger and Lotrich, 2013). In turn, cytokine release is regulated by the direct interaction of ligandbound glucocorticoid receptor (GR) to pro-inflammatory transcription factors (Wei, 1998), leading to anti-inflammatory effects on central and peripheral tissues (Coutinho and Chapman, 2011;Miller et al, 1998;Smith and Vale, 2006;Walker and Spencer, 2018). The close links between these two physiological systems, coupled with potential for long-term alterations of the HPA axis following developmental adversity, suggest that both microglia and cytokines could be potential targets for developmental programming.…”

Prenatal stress induces long-lasting effects in lung glucocorticoid receptor gene expression in a sex-dependent manner

“…On the other hand, studies with mammals have reported that exposure to maternal glucocorticoids, due to prenatal stress, may generate deleterious effects in the lung, as reduced lung function, increased lung inflammation and airway hyperreactivity [8][9][10][11]. Nonetheless, mechanisms related to lung glucocorticoid exposure of the offspring during gestation have not yet been well elucidated, although it is well known that glucocorticoid receptors (GR) function is fundamental for the maintenance of several physiological effects [6,12].…”