Hsp90aa1/JUN/Ccl2 regulatory axis mediates migration and differentiation of NSPCs, promoting the onset and progression of early post-ischemic stroke epilepsy

IF 5.1 2区 医学 Q1 NEUROSCIENCES Neurobiology of Disease Pub Date : 2024-08-10 DOI:10.1016/j.nbd.2024.106635
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Abstract

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

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Hsp90aa1/JUN/Ccl2调节轴介导NSPCs的迁移和分化,促进缺血性脑卒中后早期癫痫的发生和发展。
缺血性脑卒中后早发性癫痫是一种严重的神经系统疾病,其发病机制至今仍不完全清楚。最近的研究表明,神经干细胞/祖细胞(NSPCs)在疾病过程中起着至关重要的作用,但调控 NSPCs 的确切分子机制尚未得到深入研究。本研究利用单细胞转录组测序和生物信息学分析确定了疾病相关基因,并随后在体外和体内实验中进行了验证。研究结果显示,Hsp90aa1(热休克蛋白90 kDa alpha,A类成员1)、Jun原癌基因(JUN)和CC Motif Ligation 2(Ccl2)构成了影响NSPCs迁移和分化的重要调控轴,可能会影响缺血性中风后早发性癫痫的发病和进展。此外,研究还发现 Hsp90aa1 的表达会影响癫痫发作的可能性和脑缺血的严重程度。
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来源期刊
Neurobiology of Disease
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.
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