Zhu Chunjiao, Fan Yongmei, Peng Wenna
Department of Rehabilitation Medicine, Xiangya Second Hospital, Changsha, Hunan Province, China.
Commun Biol. 2025 Aug 13;8(1):1209. doi: 10.1038/s42003-025-08613-8.
Cerebral ischemic stroke represents a primary cause of permanent disability and mortality globally. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a prominent focus in treating a wide range of neurological disorders. In this study, we explore the role of rTMS in alleviating cerebral ischemia-reperfusion (I/R) injury by mediating Golgi apparatus (GA) stress. Here, we find that rTMS upregulates Dram1 expression and ameliorates GA stress in cerebral I/R injury in vivo and in vitro. Gli2 transcriptionally activates Dram1. HDAC5 inhibits H3K27ac modification of Gli2 promoter. rTMS promotes Gli2 expression by inhibiting HDAC5. Gli2 knockdown reverses the inhibitory effect of rTMS on OGD/R-induced neuronal GA stress. In conclusion, rTMS inhibits HDAC5-mediated deacetylation of Gli2 promoter to promote the transcriptional activation of Dram1, thereby suppressing cerebral I/R-induced GA stress. Targeting Gli2/ Dram1 axis may be an effective way to enhance the anti-ischemic stroke effect of rTMS.
脑缺血性中风是全球永久性残疾和死亡的主要原因。重复经颅磁刺激（rTMS）已成为治疗多种神经系统疾病的一个突出焦点。在本研究中，我们探讨了rTMS通过介导高尔基体（GA）应激来减轻脑缺血再灌注（I/R）损伤的作用。在此，我们发现rTMS在体内和体外均可上调Dram1表达并改善脑I/R损伤中的GA应激。Gli2转录激活Dram1。HDAC5抑制Gli2启动子的H3K27ac修饰。rTMS通过抑制HDAC5促进Gli2表达。敲低Gli2可逆转rTMS对氧糖剥夺/复氧（OGD/R）诱导的神经元GA应激的抑制作用。总之，rTMS抑制HDAC5介导的Gli2启动子去乙酰化，以促进Dram1的转录激活，从而抑制脑I/R诱导的GA应激。靶向Gli2/Dram1轴可能是增强rTMS抗缺血性中风作用的有效途径。
Eur J Med Chem. 2023-10-5
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