Age-related changes in neuroactive steroid levels in 3xTg-AD mice
Age-related changes in neuroactive steroid levels in 3xTg-AD mice
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DOI：
10.1016/j.neurobiolaging.2012.10.007
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发表时间：
2013-04-01
影响因子：
4.2
通讯作者：
Melcangi, Roberto C.
中科院分区：
文献类型：
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作者：
Caruso, Donatella;Barron, Anna M.;Melcangi, Roberto C.
尽管神经活性类固醇在包括阿尔茨海默病(AD)在内的不同神经退行性疾病的实验模型中具有神经保护作用，但它们与衰老相关的生理和病理变化的关系仍未阐明。本研究测定了青年(7月龄)和老年(24月龄)雄性野生型和三代转基因AD小鼠脑边缘区孕烯醇酮、脱氢表雄酮、孕酮、双氢孕酮、四氢孕酮、异孕酮、睾酮、双氢睾酮、5α-雄烯-3α、17β-二醇、5α-雄烯-3α、17β-二醇、17α-雌二醇和17β-雌二醇的水平。AD脑中与年龄相关的神经病理变化，如β-淀粉样蛋白堆积和胶质增生，与特定神经活性类固醇水平的改变有关，特别是与孕酮和睾酮代谢物水平的变化有关。老年AD脑内神经活性类固醇激素水平的改变可能影响经典和非经典类固醇受体(如GABA-A受体)介导的神经保护信号的激活。(C)2013 Elsevier Inc.保留所有权利。
Although neuroactive steroids exert neuroprotective actions in different experimental models of neurodegenerative diseases, including those of Alzheimer's disease (AD), their relationships with aged related physiologic and pathologic brain changes remain to be clarified. In this study the levels of pregnenolone, dehydroepiandrosterone, progesterone, dihydroprogesterone, tetrahydroprogesterone, isopregnanolone, testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-androstane-3 beta,17 beta-diol, 17 alpha-estradiol, and 17 beta-estradiol were assessed in the limbic region of young adult (7 months) and aged (24 months) male wild type and triple transgenic AD mice. Age related neuropathological changes in AD brains, such as beta-amyloid accumulation and gliosis, were associated with modified levels of specific neuroactive steroids and particularly with changes in the levels of progesterone and testosterone metabolites. The altered levels of neuroactive steroids in aged AD brains might impact on the activation of neuroprotective signaling mediated by classic and nonclassic steroid receptors, like the gamma-aminobuttyric acid (GABA)-A receptor. (C) 2013 Elsevier Inc. All rights reserved.