丹参素通过增强小鼠耳蜗神经核丛细胞中的钾电流来降低神经元的兴奋性。

IF 1.6 4区 医学 Q4 NEUROSCIENCES Neuroreport Pub Date : 2024-07-01 Epub Date: 2024-05-20 DOI:10.1097/WNR.0000000000002047
Mengfan Xu, Liqin Wang, Geng-Lin Li, Zheng-Quan Tang
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引用次数: 0

摘要

丹参素又称丹酚酸 A,是从一种传统中草药丹参(丹参)中提取的主要活性化合物。虽然丹参素的抗氧化和神经保护作用已得到充分证实,但其潜在机制却鲜为人知。在本研究中,我们试图研究丹参素是否以及如何调节中枢神经系统的神经元兴奋性和电压门控离子电流。我们制备了小鼠脑干的脑片,并对耳蜗核前腹部的丛状细胞进行了贴片钳记录。内部使用QX-314阻断Na+电流,而四乙基铵和4-氨基吡啶则用于分离不同亚型的K+电流。我们发现,100 μm 的丹参素能使灌木细胞的输入电阻降低约 60%,并使尖峰正向电压阈值移动约 7 mV,从而显著降低了兴奋性。此外,我们还发现丹参素导致兴奋性降低的原因是这些神经元中的电压门控 K+ 电流增强,其中低电压激活的 IK,A 增强了约 100%,而高电压激活的 IK,dr 则增强了约 30%。最后,我们发现丹参素对 K+ 电流的影响是剂量依赖性的,50 μm 的丹参素对 K+ 电流没有增强作用,而 200 μm 的丹参素与 100 μm 的丹参素相比,对 K+ 电流的增强作用并不明显。我们发现丹参素通过增强电压门控K+电流来降低中枢神经系统神经元的兴奋性,为其在体内广泛存在的神经保护作用提供了机理支持。
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Danshensu reduces neuronal excitability by enhancing potassium currents in bushy cells in the mouse cochlear nucleus.

Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system. We prepared brain slices of the mouse brainstem and performed patch-clamp recording in bushy cells in the anteroventral cochlear nucleus, with or without Danshensu incubation for 1 h. QX-314 was used internally to block Na+ current, while tetraethylammonium and 4-aminopyridine were used to isolate different subtypes of K+ current. We found that Danshensu of 100 μm decreased the input resistance of bushy cells by approximately 60% and shifted the voltage threshold of spiking positively by approximately 7 mV, resulting in significantly reduced excitability. Furthermore, we found this reduced excitability by Danshensu was caused by enhanced voltage-gated K+ currents in these neurons, including both low voltage-activated IK,A, by approximately 100%, and high voltage-activated IK,dr, by approximately 30%. Lastly, we found that the effect of Danshensu on K+ currents was dose-dependent in that no enhancement was found for Danshensu of 50 μm and Danshensu of 200 μm failed to cause significantly more enhancement on K+ currents when compared to that of 100 μm. We found that Danshensu reduced neuronal excitability in the central nervous system by enhancing voltage-gated K+ currents, providing mechanistic support for its neuroprotective effect widely seen in vivo.

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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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