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

To dissect the effects of corticosteroids mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR) in the central nervous system, w e compared MR-/- mice, whose salt loss syndrome was corrected by exogenous NaCl administration, with GR(-/-) mice having a brain-specific disruption o f the GR gene generated by the Cre/loxP-recombination system. Neuropatholog ical analyses revealed a decreased density of granule cells in the hippocam pus of adult MR-/- mice but not in mice with disruption of GR. Furthermore, adult MR-/- mice exhibited a significant reduction of granule cell neuroge nesis to 65% of control levels, possibly mediated by GR due to elevated cor ticosterone plasma levels. Neurogenesis was unaltered in adult mice with di sruption of GR. Thus, we could attribute long-term trophic effects of adren al steroids on dentate granule cells to MR. These MR-related alterations ma y participate in the pathogenesis of hippocampal changes observed in ageing , chronic stress and affective disorders.