小檗碱通过重塑肠道菌群相关脂质代谢减轻凯尼克酸诱导的小鼠急性癫痫发作

IF 5 1区 医学 Q1 NEUROSCIENCES
Wen-Ting Dai, Yong Zhu, Zui-Ming Jiang, Yi Xiang, Xiao-Yuan Mao, Zhao-Qian Liu
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引用次数: 0

摘要

背景:小檗碱(BBR)有减轻癫痫发作的报道。然而,其抗癫痫作用的潜在机制尚不清楚。目的本研究旨在研究BBR对kainic acid (KA)致小鼠急性癫痫发作的保护作用,并从肠道菌群分析方面进一步探讨其作用机制。材料与方法采用拉辛评分法和尼斯尔训练法评价脑缺血再灌注对急性癫痫发作的保护作用。通过16S测序和脂质组学分析BBR治疗后癫痫小鼠肠道菌群和代谢物的变化。结果BBR明显减轻ka诱导小鼠急性癫痫发作和海马神经元损伤。肠道菌群分析表明,BBR通过增加拟杆菌门(Bacteroidetes)和异普雷沃氏菌(Alloprevotella)的丰度,调节短链脂肪酸(SCFAs),减少ka诱导小鼠急性癫痫发作。脂质组学的结果还确定了结肠和海马中的21种候选代谢物,这些代谢物可能参与了BBR对急性癫痫发作的保护作用。结论BBR通过重塑结肠和海马肠道菌群相关的脂质代谢,对ka诱导的癫痫发作具有神经保护作用。BBR可作为治疗癫痫患者的一种有价值的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Berberine Alleviates Kainic Acid-Induced Acute Epileptic Seizures in Mice via Reshaping Gut Microbiota-Associated Lipid Metabolism

Berberine Alleviates Kainic Acid-Induced Acute Epileptic Seizures in Mice via Reshaping Gut Microbiota-Associated Lipid Metabolism

Background

Berberine (BBR) has been reported to mitigate epileptic seizures. However, the potential mechanism of its anti-seizure effect remains uncharacterized.

Aims

This study aimed to investigate the protective effect of BBR on acute epileptic seizures induced by kainic acid (KA) in mice and further explore its mechanism of action in the aspect of analysis of gut microbiota.

Materials and Methods

The protective effect of BBR against acute epileptic seizures was assessed via Racine score and Nissl training. Alterations of gut microbiota and metabolites in seizure mice after BBR treatment were analyzed through 16S sequencing and lipidomics, respectively.

Results

Our results showed that the BBR remarkably alleviated acute epileptic seizures and hippocampal neuron damage in KA-induced mice. The analysis of gut microbiota indicated that BBR reduced the acute epileptic seizures in KA-induced mice by increasing the abundance of Bacteroidetes and Alloprevotella, regulating short-chain fatty acids (SCFAs). Results of lipidomics also identified 21 candidate metabolites in the colon and hippocampus possibly involved in the protective effect of BBR against acute seizures.

Conclusion

These findings suggest that BBR exerts neuroprotection against KA-induced epileptic seizures through remodeling gut microbiota-associated lipid metabolism in the colon and hippocampus. BBR may serve as a valuable candidate drug for curing patients with epilepsy.

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来源期刊
CNS Neuroscience & Therapeutics
CNS Neuroscience & Therapeutics 医学-神经科学
CiteScore
7.30
自引率
12.70%
发文量
240
审稿时长
2 months
期刊介绍: CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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