Stathmin 1 regulates epileptic seizures by influencing GABAA R-mediated inhibitory synaptic activity

IF 6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2026-03-01 Epub Date: 2026-02-10 DOI:10.1016/j.nbd.2026.107310

Min Yang , Yida Hu , Junhong Wu , Hui Zhang, Juan Li, Xuefeng Wang, Xin Xu

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引用次数: 0

Abstract

Epilepsy is a common neurological disease, and approximately 30% of patients with epilepsy do not respond adequately to antiseizure medications. STMN1 (Stathmin 1) is a potent regulator of microtubule stability, and previous research has shown that STMN1 expression is increased in epileptic brain. However, the effect of STMN1 on epileptic seizures remains unclear. Our study found that STMN1 expression was associated with GABA_A receptor (GABA_AR), inhibitory GABAergic neurons and the inhibitory postsynaptic scaffold protein gephyrin. STMN1 downregulation decreased the susceptibility to epileptic seizures in a kainic acid–induced model and pentylenetetrazole-induced kindling model of epilepsy, whereas the overexpression of STMN1 showed opposite effects. More specifically, whole-cell patch-clamp recordings indicate that STMN1 regulated inhibitory synaptic transmission, potentially due to STMN1-mediated postsynaptic GABA_AR transport. These results provides the demonstration that STMN1 plays a critical role in the regulation of epileptic seizures, suggesting a molecular mechanism for new therapeutic strategies.

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安定素1通过影响GABAA r介导的抑制性突触活性调控癫痫发作。

癫痫是一种常见的神经系统疾病，大约30%的癫痫患者对抗癫痫药物反应不充分。STMN1 （Stathmin 1）是一种有效的微管稳定性调节剂，先前的研究表明，STMN1在癫痫脑中的表达增加。然而，STMN1对癫痫发作的影响尚不清楚。我们的研究发现STMN1的表达与GABAA受体（GABAAR）、抑制性GABAA能神经元和抑制性突触后支架蛋白gephyrin有关。在kainic酸诱导的癫痫模型和戊四唑诱导的癫痫模型中，STMN1下调可降低癫痫发作的易感性，而STMN1过表达则表现出相反的作用。更具体地说，全细胞膜片钳记录表明STMN1调节抑制性突触传递，可能是由于STMN1介导的突触后GABAAR运输。这些结果证明STMN1在癫痫发作的调控中起着关键作用，为新的治疗策略提供了分子机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.