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Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice
Author(s) -
Gass Peter,
Kretz Oliver,
Wolfer David P,
Berger Stefan,
Tronche Francois,
Reichardt Holger M,
Kellendonk Christoph,
Lipp HansPeter,
Schmid Wolfgang,
Schütz Günther
Publication year - 2000
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvd088
Subject(s) - neurogenesis , mineralocorticoid receptor , endocrinology , medicine , hippocampal formation , granule cell , glucocorticoid receptor , corticosterone , biology , mineralocorticoid , glucocorticoid , hippocampus , dentate gyrus , central nervous system , neuroscience , hormone , aldosterone
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.