Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice
Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice
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DOI：
10.1093/embo-reports/kvd088
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发表时间：
2000-11-01
期刊：
影响因子：
7.7
通讯作者：
Schütz, G
中科院分区：
文献类型：
--
作者：
Gass, P;Kretz, O;Schütz, G
为了剖析中枢神经系统中盐皮质激素 (MR) 和糖皮质激素受体 (GR) 介导的皮质类固醇的作用，我们将 MR-/- 小鼠（其盐丢失综合征通过外源性 NaCl 给药纠正）与 GR(-/-) 小鼠进行了比较，GR(-/-) 小鼠的脑部特异性破坏了由 Cre/loxP 重组系统产生的 GR 基因。神经病理学分析显示，成年 MR-/- 小鼠海马中颗粒细胞密度降低，但 GR 破坏的小鼠则没有。此外，成年 MR-/- 小鼠表现出颗粒细胞神经发生显着减少至对照水平的 65%，这可能是由于皮质酮血浆水平升高而由 GR 介导的。 GR 破坏后，成年小鼠的神经发生未发生改变。因此，我们可以将肾上腺类固醇对齿状颗粒细胞的长期营养作用归因于 MR。这些与 MR 相关的改变可能参与了在衰老、慢性应激和情感障碍中观察到的海马变化的发病机制。
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.