Brain mineralocorticoid receptor: The other one

Abstract

For many years the glucocorticoid receptor – mediating slow genomic actions – was considered to be the stress receptor in the brain, since intracellular mineralocorticoid receptors (MRs) are already considerably occupied under rest and thus not available for corticosteroids. A decade ago it was discovered that pyramidal cells e.g. in the hippocampus and basolateral amygdala also respond quickly to corticosterone, via nongenomically acting MRs that require a tenfold higher concentration than MRs acting through genomic signaling. Subsequent behavioral studies in humans and rodents have shown that these rapid MR-mediated actions are important for an appropriate quick response to a stressful condition. It is now thought that directly after stress onset MRs mediate a shift in resources towards striatal regions, at the cost of the hippocampus and prefrontal cortex. Behaviorally this is reflected in heightened attention and reverting to the use of more simple strategies e.g. in spatial or fear learning. This is highly adequate in the given situation: blockade of MRs impairs overall behavioral performance. Also in the face of prolonged adversity (chronic unpredictable stress) or stress during critical developmental windows (fragmented maternal care during the first postnatal week) do MRs exert beneficial effects, since forebrain-specific MR overexpression can rescue behavioral impairment seen after such conditions in wildtype animals. The brain MR is therefore not only essential for an appropriate neuronal and behavioral response during acute stress conditions but also beneficial in more severe stress conditions that are known to be a risk factor for psychopathology in humans.