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首页> 外文期刊>Brain research >Dehydroepiandrosterone administration improves memory deficits following transient brain ischemia through sigma-1 receptor stimulation
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Dehydroepiandrosterone administration improves memory deficits following transient brain ischemia through sigma-1 receptor stimulation

机译：脱氢表雄酮给药可通过sigma-1受体刺激改善短暂性脑缺血后的记忆缺陷

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摘要

Dehydroepiandrosterone (DHEA) is the most abundant neurosteroid synthesized de novo in the central nervous system. Oral DHEA administration elicits neuroprotection and cognitive improvement, but mechanisms underlying these functions in cerebral ischemia have remained unclear. Since DHEA is the endogenous ligand for the sigma-1 receptor (sigma 1R), we determined whether oral DHEA administration prevents neuronal cell death and improves cognition via sigma 1R stimulation in brain ischemia using a 20-min bilateral common carotid artery occlusion (BCCAO) mouse model. Twenty-four hours after BCCAO ischemia, mice were administered DHEA (15 or 30 mg/kg p.o.) daily for 11 consecutive days. Memory deficits following brain ischemia were improved by DHEA administration dose-dependently. Accordingly, DHEA administration significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice. Interestingly, DHEA administration rescued decreases in Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in the CA1 region. Moreover, DHEA administration significantly ameliorated decreases in adenosine 5'-triphosphate (ATP) levels and decreased sigma 1R expression levels in CA1 following BCCAO ischemia. Finally, co-treatment of mice with the sigma 1R antagonist NE-100 (1 mg/kg, p.o.) blocked DHEA effects on memory improvement and neuroprotection in ischemic mice. Taken together, DHEA prevents neuronal cell death and activates CaMKII via sigma 1R stimulation, thereby improving cognitive deficits following brain ischemia. (C) 2015 Elsevier B.V. All rights reserved.
机译：脱氢表雄酮（DHEA）是中枢神经系统中从头合成的最丰富的神经类固醇。口服脱氢表雄酮（DHEA）给药可引起神经保护和认知功能改善，但这些功能在脑缺血中的作用机制仍不清楚。由于DHEA是sigma-1受体（sigma 1R）的内源性配体，因此我们确定口服DHEA是否通过使用20分钟的双边颈总动脉闭塞（BCCAO）在脑缺血中通过sigma 1R刺激来预防神经元细胞死亡并改善认知鼠标模型。 BCCAO缺血后二十四小时，每天连续11天每天给小鼠施用DHEA（15或30 mg / kg p.o.）。 DHEA剂量依赖性地改善了脑缺血后的记忆缺陷。因此，DHEA给药显着预防了BCCAO小鼠海马CA1区的神经元细胞死亡。有趣的是，DHEA给药挽救了Ca2 + /钙调蛋白依赖性蛋白激酶II（CaMKII）自磷酸化以及CA1区细胞外信号调节激酶（ERK）和蛋白激酶B（Akt）磷酸化的降低。此外，在BCCAO缺血后，DHEA的给药显着改善了CA1中腺苷5'-三磷酸（ATP）水平的降低和sigma 1R表达水平的降低。最后，用sigma 1R拮抗剂NE-100（1 mg / kg，p.o.）共处理小鼠可阻断DHEA对缺血小鼠的记忆改善和神经保护作用。总之，DHEA可以防止神经元细胞死亡并通过sigma 1R刺激激活CaMKII，从而改善脑缺血后的认知缺陷。 （C）2015 Elsevier B.V.保留所有权利。

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