氟伐他汀是一种HMG-CoA还原酶抑制剂,通过提高癫痫发作阈值和调节胚胎大鼠皮层神经元的膜兴奋性,对nmda诱导的癫痫发作具有保护作用。

IF 2.7 4区 医学 Q3 NEUROSCIENCES
Ya-Jean Wang , Eric Hwang , Hwei-Hsien Chen , Ming-Huan Chan , Che-Jui Yeh , You-Xuan Liu , Chieh-Min Huang
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引用次数: 0

摘要

背景:全世界有近5000万人患有癫痫。先前的研究表明,他汀类药物对几种神经病理状况有神经保护作用。然而,氟伐他汀是否能够改变与NMDA受体激活介导的神经元兴奋性和进展相关的癫痫发作类型尚不清楚,并且这些作用所涉及的机制迄今尚未完全了解。本研究评估了氟伐他汀对NMDA诱导的癫痫发作、BKCa通道活性、NMDA受体激活打开的BKCa电流、钠通道电流、NMDA受体介导的电流以及与NMDA受体激活相关的超兴奋神经元活性的影响。方法:观察氟伐他汀对NMDA诱导的小鼠癫痫发作阈值的影响。采用细胞贴壁法和全细胞膜片钳法记录rCN和SHSY5Y神经母细胞瘤细胞的离子电流和动作电位。结果:本研究结果表明氟伐他汀确实增加了NMDA诱导的癫痫发作阈值,抑制了NMDA诱导的动作电位频率。值得注意的是,我们的研究结果提供了氟伐他汀对rCN和SHSY5Y神经母细胞瘤细胞中NMDA受体介导的电流、BKCa通道电流、NMDA受体激活打开的BKCa电流和钠通道电流具有抑制作用的证据。结论:氟伐他汀可能通过抑制NMDA介导的动作电位、NMDA受体介导的电流、BKCa通道和钠通道,对神经元兴奋性和NMDA受体激活相关的癫痫发作类型有保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Fluvastatin, an HMG-CoA reductase inhibitor, exerts protective effect against NMDA-induced seizure by increasing the seizure threshold and modulating membrane excitability in embryonic rat cortical neuron

Fluvastatin, an HMG-CoA reductase inhibitor, exerts protective effect against NMDA-induced seizure by increasing the seizure threshold and modulating membrane excitability in embryonic rat cortical neuron

Background

Epilepsy affects nearly 50 million people worldwide. Previous studies have indicated the neuroprotective effects of statin on several neuropathological conditions. However, it is very much unknown whether fluvastatin was able to alter the seizure types related to neuronal excitability and progression mediated by NMDA receptor activation, and the mechanisms involved in these actions are not completely understood so far. Our study evaluated the effects of fluvastatin on the NMDA-induced seizure, BKCa channels activity, NMDA receptor activation opens BKCa current, sodium channel current, NMDA receptor-mediated current, and hyperexcitable neuronal activity associated with activation of NMDA receptor.

Methods

The effects of fluvastatin on seizure thresholds induced by NMDA were monitored in mice. The cell-attached and whole-cell patch-clamp recordings were applied to evaluate the ionic currents and action potentials of rCN or SHSY5Y neuroblastoma cells.

Results

The results of our study have demonstrated that fluvastatin did increase the NMDA-induced seizure threshold and suppressed the frequency of action potentials induced by NMDA. Notably, our findings provide the evidence that fluvastatin exhibits inhibitory effects on NMDA receptor-mediated current, BKCa channels currents, NMDA receptor activation opens BKCa current, and sodium channel currents in rCN and SHSY5Y neuroblastoma cells.

Conclusion

Our findings suggested that fluvastatin may protect against seizure types related to neuronal excitability and NMDA receptor activation by inhibiting NMDA-mediated action potentials, NMDA receptor-mediated currents, BKCa channels, and sodium channels.
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来源期刊
Brain Research
Brain Research 医学-神经科学
CiteScore
5.90
自引率
3.40%
发文量
268
审稿时长
47 days
期刊介绍: An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
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