甲基CpG结合结构域3在癫痫发作和癫痫发生中的作用。

IF 1.4 4区 医学 Q4 NEUROSCIENCES
Karolina Niźinska, Maciej Olszewski, Dorota Nowicka, Kinga Szydłowska, Kinga Nazaruk, Katarzyna Łukasiuk
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引用次数: 0

摘要

甲基CpG结合域蛋白3 (Mbd3)是NuRD染色质重塑复合体的一个组成部分,在转录调控中起作用,并与神经元发育有关;然而,它在癫痫中的作用仍不清楚。本研究利用编码短发夹RNA的腺相关病毒载体下调基底外侧杏仁核中Mbd3的表达,研究Mbd3下调对大鼠癫痫易感性和行为的影响。行为学评价包括开场试验、升高+迷宫试验和超兴奋性试验。采用PTZ激发模型和PTZ点燃模型评估癫痫易感性。Mbd3水平的降低显著增加了PTZ挑战中癫痫发作的潜伏期,表明癫痫发作阈值升高。Mbd3表达降低的大鼠在野外测试中也表现出增加的焦虑样行为。在PTZ点火模型中,Mbd3下调不影响癫痫发生的进展。这些发现表明Mbd3对癫痫的急性发作易感性和情绪行为有影响,但对癫痫的长期发展没有影响,突出了其作为癫痫发作调节的表观遗传调节剂的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of methyl‑CpG binding domain 3 in seizures and epileptogenesis.

Methyl‑CpG binding domain protein 3 (Mbd3), a component of the NuRD chromatin remodeling complex, plays a role in transcriptional regulation and has been implicated in neuronal development; however, its role in epilepsy remains unclear. This study investigated the effects of Mbd3 downregulation on seizure susceptibility and behavior in rats, using adeno‑associated viral vectors that code for short hairpin RNA to downregulate Mbd3 expression in the basolateral amygdala. Behavioral assessments included the open field test, elevated plus maze test, and hyperexcitability test. Seizure susceptibility was evaluated using the PTZ challenge and PTZ kindling models. A decreased Mbd3 level significantly increased latency to seizure onset in the PTZ challenge, indicating a raised seizure threshold. Rats with reduced Mbd3 expression also exhibited increased anxiety‑like behavior in the open‑field test. Mbd3 downregulation did not affect the progression of epileptogenesis in the PTZ kindling model. These findings suggest that Mbd3 contributes to acute seizure susceptibility and emotional behavior but not to the long‑term development of epilepsy, highlighting its potential as an epigenetic modulator in seizure regulation.

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来源期刊
CiteScore
2.20
自引率
7.10%
发文量
40
审稿时长
>12 weeks
期刊介绍: Acta Neurobiologiae Experimentalis (ISSN: 0065-1400 (print), eISSN: 1689-0035) covers all aspects of neuroscience, from molecular and cellular neurobiology of the nervous system, through cellular and systems electrophysiology, brain imaging, functional and comparative neuroanatomy, development and evolution of the nervous system, behavior and neuropsychology to brain aging and pathology, including neuroinformatics and modeling.
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