Insights into isoform-specific mineralocorticoid receptor action in the hippocampus

The mineralocorticoid receptor (MR) plays a critical role in the mammalian brain as a mediator of appropriate cellular and behavioural responses under both baseline and stressful conditions. In the hippocampus, the MR has been implicated in several processes, such as neuronal maintenance, adult neurogenesis, inhibitory control of the hypothalamic-pituitary-adrenal axis, and learning and memory. Because of its high affinity for endogenous glucocorticoid hormones, the MR has long been postulated to mediate tonic actions in the brain, but more recent data have expanded on this view, indicating that the MR elicits dynamic responses as well. The complexity of the diverse molecular, cellular, and physiological functions fulfilled by the human, rat and mouse MR could at least partially be explained by the existence of different isoforms of the receptor. The structural and functional characteristics of these isoforms, however, have remained largely unexplored. The present article will review the current knowledge concerning human, rat, and mouse MR isoforms and evaluate seminal studies concerning the roles of the brain MR, with the intent to shed light on the function of its specific isoforms.

Automated summary

The mineralocorticoid receptor (MR) is essential for appropriate brain responses under normal and stressful conditions, specifically in processes related to neuronal maintenance, neurogenesis, hormone regulation, and cognitive function. The high affinity of MR for glucocorticoid hormones suggests its involvement in tonic brain actions, but recent studies have also demonstrated its dynamic responses. However, the understanding of the structure and function of MR isoforms in humans, rats, and mice remains limited.