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

Abstract 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...

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Autores principales: Juan Chen, Rong Hu, Huabao Liao, Ya Zhang, Ruixue Lei, Zhifeng Zhang, Yang Zhuang, Yu Wan, Ping Jin, Hua Feng, Qi Wan
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/70b56126228b48c491e3480be28700cd
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spelling oai:doaj.org-article:70b56126228b48c491e3480be28700cd2021-12-02T15:04:57ZA non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury10.1038/s41598-017-03909-02045-2322https://doaj.org/article/70b56126228b48c491e3480be28700cd2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03909-0https://doaj.org/toc/2045-2322Abstract 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.Juan ChenRong HuHuabao LiaoYa ZhangRuixue LeiZhifeng ZhangYang ZhuangYu WanPing JinHua FengQi WanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Juan Chen
Rong Hu
Huabao Liao
Ya Zhang
Ruixue Lei
Zhifeng Zhang
Yang Zhuang
Yu Wan
Ping Jin
Hua Feng
Qi Wan
A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
description Abstract 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.
format article
author Juan Chen
Rong Hu
Huabao Liao
Ya Zhang
Ruixue Lei
Zhifeng Zhang
Yang Zhuang
Yu Wan
Ping Jin
Hua Feng
Qi Wan
author_facet Juan Chen
Rong Hu
Huabao Liao
Ya Zhang
Ruixue Lei
Zhifeng Zhang
Yang Zhuang
Yu Wan
Ping Jin
Hua Feng
Qi Wan
author_sort Juan Chen
title A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
title_short A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
title_full A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
title_fullStr A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
title_full_unstemmed A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
title_sort non-ionotropic activity of nmda receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/70b56126228b48c491e3480be28700cd
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