Brain Mineralocorticoid receptor in health and disease: from molecular
signaling to cognitive and emotional function
Abstract
Brain mineralocorticoid receptors (MR) mediate effects of aldosterone in
relation to salt homeostasis, and of glucocorticoid stress hormones
corticosteroids in the context of stress adaptation. Brain stem MRs
respond to aldosterone, while forebrain MRs mediate rapid and delayed
MR-mediated glucocorticoids effects in conjunction with the
glucocorticoid receptor. MR-mediated effects depend on gender, genetic
variations and environmental influences. Disturbed MR activity by
chronic stress or in certain (endocrine) diseases can cause deleterious
effects on affective state, cognitive and behavioural function in
susceptible individuals. High MR activation may have protective effects
in healthy individuals, whereas dysregulated high MR activity during a
stress response would require treatment with mineralocorticoid receptor
antagonists (MRAs). Here, we discuss recent pharmacological and genetic
developments, from the molecular underpinnings of MR signaling and
function, to pharmacological interventions in the clinic. Improved
understanding of MR dependent pathways will help to improve
glucocorticoid therapy, unwanted side effects and psychiatric symptoms.