Transcranial direct-current stimulation protects against cerebral ischemia-reperfusion injury through regulating Cezanne-dependent signaling

被引：28

作者：

Cheng, Jing ^{[1
]}

Fan, Yan-Qin ^{[2
]}

Jiang, Hong-Xiang ^{[1
]}

Chen, Song-Feng ^{[3
]}

Chen, Juan ^{[4
]}

Liao, Xin-Yu ^{[5
]}

Zou, Ying-Ying ^{[5
]}

Lan, Hai-yang ^{[6
]}

Cui, Yu ^{[7
]}

Chen, Zhi-Biao ^{[1
]}

Chen, Qian-Xue ^{[1
]}

Wan, Qi ^{[7
]}

机构：

[1] Wuhan Univ, Renmin Hosp, Dept Neurosurg, 99 Zhang Zhidong St, Wuhan 430060, Peoples R China

[2] Wuhan Univ, Renmin Hosp, Dept Nephrol, 99 Zhang Zhidong St, Wuhan 430060, Peoples R China

[3] Wuhan Univ, Sch Med, Dept Physiol, 185 Donghu St, Wuhan 430071, Peoples R China

[4] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Neurol, 26 Shengli St, Wuhan 430013, Peoples R China

[5] Kunming Med Univ, Fac Basic Med Sci, Dept Pathol & Pathophysiol, 1168 West Chunrong Rd, Kunming 650500, Yunnan, Peoples R China

[6] Army Med Univ, Daping Hosp, Army Med Ctr, Dept Orthopaed, Chongqing 400042, Peoples R China

[7] Qingdao Univ, Inst Neuroregenerat & Neurorehabil, Dept Pathophysiol, 308 Ningxia St, Qingdao 266071, Peoples R China

来源：

EXPERIMENTAL NEUROLOGY | 2021年 / 345卷

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

Transcranial direct-current stimulation; Ischemic stroke; Cerebral ischemia-reperfusion injury; Cezanne; SIRT6; DNA DSB; ISCHEMIA/REPERFUSION INJURY; SIRTUIN; 6; STROKE; REPAIR; BRAIN; SAFETY; MODEL;

D O I：

10.1016/j.expneurol.2021.113818

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons.

引用

页数：11

共 42 条

[1]

Cezanne/OTUD7B is a cell cycle-regulated deubiquitinase that antagonizes the degradation of APC/C substrates [J].