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首页> 外文期刊>BMC Neuroscience >Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential
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Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential

机译：阿洛培那诺酮诱导的胚胎海马神经元细胞内钙升高与其增殖潜能平行

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Background Factors that regulate intracellular calcium concentration are known to play a critical role in brain function and neural development, including neural plasticity and neurogenesis. We previously demonstrated that the neurosteroid allopregnanolone (APα; 5α-pregnan-3α-ol-20-one) promotes neural progenitor proliferation in vitro in cultures of rodent hippocampal and human cortical neural progenitors, and in vivo in triple transgenic Alzheimer's disease mice dentate gyrus. We also found that APα-induced proliferation of neural progenitors is abolished by a calcium channel blocker, nifedipine, indicating a calcium dependent mechanism for the proliferation. Methods In the present study, we investigated the effect of APα on the regulation of intracellular calcium concentration in E18 rat hippocampal neurons using ratiometric Fura2-AM imaging. Results Results indicate that APα rapidly increased intracellular calcium concentration in a dose-dependent and developmentally regulated manner, with an EC50 of 110 ± 15 nM and a maximal response occurring at three days in vitro . The stereoisomers 3β-hydroxy-5α-hydroxy-pregnan-20-one, and 3β-hydroxy-5β-hydroxy-pregnan-20-one, as well as progesterone, were without significant effect. APα-induced intracellular calcium concentration increase was not observed in calcium depleted medium and was blocked in the presence of the broad spectrum calcium channel blocker La3+, or the L-type calcium channel blocker nifedipine. Furthermore, the GABAA receptor blockers bicuculline and picrotoxin abolished APα-induced intracellular calcium concentration rise. Conclusion Collectively, these data indicate that APα promotes a rapid, dose-dependent, stereo-specific, and developmentally regulated increase of intracellular calcium concentration in rat embryonic hippocampal neurons via a mechanism that requires both the GABAA receptor and L-type calcium channel. These data suggest that APα-induced intracellular calcium concentration increase serves as the initiation mechanism whereby APα promotes neurogenesis.
机译：背景技术已知调节细胞内钙浓度的因素在脑功能和神经发育（包括神经可塑性和神经发生）中起关键作用。我们以前证明了神经甾体allopregnanolone（APα;5α-pregnan-3α-ol-20-one）在啮齿类海马和人类皮层神经祖细胞的培养物中以及体外在三重转基因阿尔茨海默氏病小鼠的齿状回中促进神经祖细胞增殖。我们还发现，钙通道阻滞剂硝苯地平消除了APα诱导的神经祖细胞增殖，表明钙依赖的增殖机制。方法在本研究中，我们使用比例Fura2-AM成像技术研究了APα对E18大鼠海马神经元细胞内钙浓度的调节作用。结果结果表明，APα以剂量依赖性和发育调控的方式迅速增加细胞内钙浓度，EC 50 为110±15 nM，体外反应三天达到最大响应。立体异构体3β-羟基-5α-羟基-pregnan-20-one和3β-羟基-5β-羟基-pregnan-20-one和黄体酮均无明显作用。在贫钙培养基中未观察到APα诱导的细胞内钙浓度增加，在存在广谱钙通道阻滞剂La 3 + 或L型钙通道阻滞剂硝苯地平的情况下被阻止。此外，GABA A 受体阻滞剂双小分子和微毒素消除了APα诱导的细胞内钙浓度升高。结论总的来说，这些数据表明，APα通过同时需要GABA A 受体的机制促进大鼠胚胎海马神经元细胞内钙浓度的快速，剂量依赖性，立体特异性和发育调控的增加。和L型钙通道。这些数据表明，APα诱导的细胞内钙浓度增加是APα促进神经发生的起始机制。

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