Figure legends
Figure 1. The HPA axis: CRH (and AVP) are secreted from the PVN. These hormones in turn, stimulate the secretion of ACTH from the anterior pituitary, which in turn, drives the secretion of glucocorticoids (cortisol or corticosterone) from the adrenal cortex. Aldosterone selective MRs that mediate behaviours involved in salt appetite are mostly located in neurons of the nucleus tractus solitarii (NTS) and the circumventricular organs. The MR-NTS neurons innervate to limbic forebrain regions, notably the hippocampus and locus coeruleus areas involved in arousal where they reciprocally modulate pathways involved in emotions, memory performance, and reward processing. Created with BioRender.com
Figure 2. In the blood Cortisol (CORT) circulates at 1000-fold higher concentrations than aldosterone (ALDO), but bind with equally high affinity to the MR. This CORT:ALDO ratio is more profound in the brain, which in MR-expressing cells results in CORT occupied MRs, restricting binding by ALDO. However, ALDO selective cells express 11-hydroxysteroid dehydrogenase type 2 (11HSD-2) which converts CORT into its inactive keto variant cortisone. Upon ligand binding, nuclear translocation of MR occurs, enabling rapid non-genomic effects or DNA binding at targeted sequences to exert genomic effects. Created with BioRender.com
Figure 3. Hypothetical model of MR activity in patients with major depressive disorder and healthy individuals and the potential effects of MR blockade.