Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice

Abstract

To dissect the effects of corticosteroids mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR) in the central nervous system, we compared MR(–/–) mice, whose salt loss syndrome was corrected by exogenous NaCl administration, with GR(–/–) mice having a brain-specific disruption of the GR gene generated by the Cre/loxP-recombination system. Neuropathological analyses revealed a decreased density of granule cells in the hippocampus of adult MR(–/–) mice but not in mice with disruption of GR. Furthermore, adult MR(–/–) mice exhibited a significant reduction of granule cell neurogenesis to 65% of control levels, possibly mediated by GR due to elevated corticosterone plasma levels. Neurogenesis was unaltered in adult mice with disruption of GR. Thus, we could attribute long-term trophic effects of adrenal steroids on dentate granule cells to MR. These MR-related alterations may participate in the pathogenesis of hippocampal changes observed in ageing, chronic stress and affective disorders