Contrasting Roles of Corticosteroid Receptors in Hippocampal Plasticity

Abstract

Elevated levels of corticosteroid hormones, presumably occupying both mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs), have been reported to impair synaptic plasticity in the hippocampus as well as the acquisition of hippocampus-dependent memories. In contrast, recent evidence suggests that activation of MRs enhance cognitive functions. To clarify the roles of different steroid receptors in hippocampal plasticity, young adult rats were injected with the GR antagonist RU38486 (mifepristone) or the MR antagonist Spironolactone before the exposure to an acute swim stress. Hippocampal responses to perforant path stimulation were then recorded in anesthetized rats. Stress combined with RU38486 produced a striking facilitation of LTP. Spironolactone enabled only short-term potentiation that reversed to long-term depression (LTD) in the stressed animals. Finally, the blockade of both MRs and GRs led to impairment of long-term potentiation. These findings indicate that MRs and GRs assume opposite roles in regulation of synaptic plasticity after acute exposure to stressors.

Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice

“…In other cell types that lack 11βHSD2 such as neurons, MR and GR play opposing cellular roles through independent but overlapping mechanisms (35,36). We observed a similar role in macrophages, where MR and GR can drive opposite polarizing responses, largely through independent mechanisms.…”

“…In addition, MR has long been known to coordinate the cellular response to glucocorticoids in tissues lacking 11βHSD2, such as the brain, where MR controls an overlapping counterregulatory program against the actions of GR (35,36). In macrophages, MR and GR also have largely opposing roles, and the effects of MR are independent of GR.…”

Differential Corticosteroid Modulation of Inhibitory Synaptic Currents in the Dorsal and Ventral Hippocampus

“…Yet, a clear picture of the main actions of corticosterone on synaptic interactions and its relations to the ability to express LTP in the hippocampus is still missing. The fact that such an interaction is complex is illustrated in a recent study, where, following an exposure to acute swim stress, the activation of MRs produced an enhancement of LTP in the perforant path of the dentate gyrus, whereas following activation of GRs before the stressful experience an impairment in LTP was found (Avital et al, 2006). These studies suggest that MRs and GRs assume opposite roles in the regulation of synaptic plasticity after an acute exposure to stressors.…”

Effect of chronic prenatal restraint stress on hippocampal neuronal cell density in male and female wistar rats at weaning

“…Elevated levels of corticosteroid hormones on MRs and GRs assume opposite roles in regulation of synaptic plasticity after acute exposure to stressors (De Kloet, et al 1987). Glucocorticoids (GCs) are secreted by the adrenal cortex and mediate adaptation to acute stress (Avi Avital et al, 2006). Chronic GC exposure as a result of prolonged stress or pathological GC hypersecretion can be profoundly deleterious, due to the catabolic effects of the hormone's actions (Avi Avital et al, 2006 andMunck et al, 1984).…”

“…Glucocorticoids (GCs) are secreted by the adrenal cortex and mediate adaptation to acute stress (Avi Avital et al, 2006). Chronic GC exposure as a result of prolonged stress or pathological GC hypersecretion can be profoundly deleterious, due to the catabolic effects of the hormone's actions (Avi Avital et al, 2006 andMunck et al, 1984). Glucocorticoids are very liposoluble and easily cross placental and blood-brain barrier (Krieger 1982).…”