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

被引:123
作者
Gass, P
Kretz, O
Wolfer, DP
Berger, S
Tronche, F
Reichardt, HM
Kellendonk, C
Lipp, HP
Schmid, W
Schütz, G [1 ]
机构
[1] German Canc Res Ctr, Div Mol Biol Cell 1, Heidelberg, Germany
[2] Cent Inst Mental Hlth ZI, D-68159 Mannheim, Germany
[3] Univ Zurich, Dept Anat, CH-8057 Zurich, Switzerland
关键词
D O I
10.1093/embo-reports/kvd088
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页码:447 / 451
页数:5
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