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.