A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury

被引：42

作者：

Chen, Juan ^{[1
,2
]}

Hu, Rong

Liao, Huabao ^{[1
]}

Zhang, Ya ^{[1
]}

Lei, Ruixue ^{[1
]}

Zhang, Zhifeng ^{[1
]}

Zhuang, Yang ^{[1
]}

Wan, Yu ^{[1
]}

Jin, Ping ^{[2
]}

Feng, Hua ^{[3
]}

Wan, Qi ^{[1
,4
]}

机构：

[1] Wuhan Univ, Collaborat Innovat Ctr Brain Sci, Sch Med, Dept Physiol,Sch Basic Med Sci, 185 Donghu St, Wuhan 430071, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Dept Neurol, Tongji Med Coll, Cent Hosp Wuhan, 26 Shengli St, Wuhan 430014, Peoples R China

[3] Southwest Hosp, Dept Neurosurg, Chongqing 400038, Peoples R China

[4] Qingdao Univ, Sch Med, Inst Neuroregenerat & Neurorehabil, 308 Ningxia St, Qingdao 266071, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

SRC FAMILY KINASES; ARTERY OCCLUSION; SUBUNITS; ACTIVATION; INHIBITION; STROKE; CORD; RATS; TERM; STRYCHNINE;

D O I：

10.1038/s41598-017-03909-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

NMDA receptor (NMDAR) is known for its ionotropic function. But recent evidence suggests that NMDAR also has a non-ionotropic property. To determine the role of non-ionotropic activity of NMDARs in clinical relevant conditions, we tested the effect of glycine, a co-agonist of NMDARs, in rat middle cerebral artery occlusion (MCAO), an animal model of cerebral ischemia-reperfusion injury after the animals were injected with the NMDAR channel blocker MK-801 and the glycine receptor antagonist strychnine. We show that glycine reduces the infarct volume in the brain of ischemic stroke animals pre-injected with MK-801 and strychnine. The effect of glycine is sensitive to the antagonist of glycine-GluN1 binding site and blocked by Akt inhibition. In the neurobehavioral tests, glycine improves the functional recovery of stroke animals pre-injected with MK-801 and strychnine. This study suggests that glycine-induced neuroprotection is mediated in part by the non-ionotropic activity of NMDARs via Akt activation in cerebral ischemia-reperfusion injury.

引用

页数：14

共 52 条

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