Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke

Background: Evidences indicate that exosomes-mediated delivery of microRNAs (miRNAs or miRs) is involved in the neurogenesis of stroke. This study was to investigate the role of exosomal miRNAs in non-drug therapy of electro-acupuncture (EA) regulating endogenous neural stem cells for stroke recover...

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Main Authors: Shenghang Zhang, Tingting Jin, Lulu Wang, Weilin Liu, Yuhao Zhang, Yi Zheng, Yunjiao Lin, Minguang Yang, Xiaojun He, Huawei Lin, Lidian Chen, Jing Tao
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-07-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fncel.2020.00223/full
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author Shenghang Zhang
Shenghang Zhang
Tingting Jin
Lulu Wang
Weilin Liu
Yuhao Zhang
Yi Zheng
Yunjiao Lin
Minguang Yang
Xiaojun He
Huawei Lin
Lidian Chen
Jing Tao
author_facet Shenghang Zhang
Shenghang Zhang
Tingting Jin
Lulu Wang
Weilin Liu
Yuhao Zhang
Yi Zheng
Yunjiao Lin
Minguang Yang
Xiaojun He
Huawei Lin
Lidian Chen
Jing Tao
author_sort Shenghang Zhang
collection DOAJ
description Background: Evidences indicate that exosomes-mediated delivery of microRNAs (miRNAs or miRs) is involved in the neurogenesis of stroke. This study was to investigate the role of exosomal miRNAs in non-drug therapy of electro-acupuncture (EA) regulating endogenous neural stem cells for stroke recovery.Methods: The model of focal cerebral ischemia and reperfusion in rats were established by middle cerebral artery occlusion (MCAO) and treated by EA. The exosomes were extracted from peri-ischemic striatum and identified by exosomal biomarkers, and detected differentially expressed miRNAs with microarray chip. Primary stem cells were cultured, and oxygen–glucose deprivation and reperfusion (OGD/R) was used to mimic vitro ischemic injury.Results: The levels of exosomal biomarkers TSG101 and CD81 were increased in peri-ischemic striatum after EA treatment, and we revealed 25 differentially expressed miRNAs in isolated exosomes, of which miR-146b was selected for further analysis, and demonstrated that EA increased miR-146b expression and its inhibitors could block the effects. Subsequently, we confirmed that EA upregulated miR-146b expression to promote neural stem cells differentiation into neurons in peri-ischemic striatum. In vitro, it was verified that OGD/R hindered neural stem cells differentiation, and miR-146b inhibitors furtherly suppressed its differentiation, simultaneously NeuroD1 was involved in neural stem cells differentiation into neurons. Moreover, in vivo we found EA promoted NeuroD1-mediated neural stem cells differentiation via miR-146b. In addition, EA also could improve neurological deficits through miR-146b after ischemic stroke.Conclusion: EA promotes the differentiation of endogenous neural stem cells via exosomal miR-146b to improve neurological injury after ischemic stroke.
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spelling doaj.art-b790b42dbbee4352b3d248dc17fd3a7f2022-12-22T01:20:25ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-07-011410.3389/fncel.2020.00223546584Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic StrokeShenghang Zhang0Shenghang Zhang1Tingting Jin2Lulu Wang3Weilin Liu4Yuhao Zhang5Yi Zheng6Yunjiao Lin7Minguang Yang8Xiaojun He9Huawei Lin10Lidian Chen11Jing Tao12College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaThe 900 Hospital of the Joint Logistic Team, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaFujian University of Traditional Chinese Medicine, The Academy of Rehabilitation Industry, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaFujian University of Traditional Chinese Medicine, The Academy of Rehabilitation Industry, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaBackground: Evidences indicate that exosomes-mediated delivery of microRNAs (miRNAs or miRs) is involved in the neurogenesis of stroke. This study was to investigate the role of exosomal miRNAs in non-drug therapy of electro-acupuncture (EA) regulating endogenous neural stem cells for stroke recovery.Methods: The model of focal cerebral ischemia and reperfusion in rats were established by middle cerebral artery occlusion (MCAO) and treated by EA. The exosomes were extracted from peri-ischemic striatum and identified by exosomal biomarkers, and detected differentially expressed miRNAs with microarray chip. Primary stem cells were cultured, and oxygen–glucose deprivation and reperfusion (OGD/R) was used to mimic vitro ischemic injury.Results: The levels of exosomal biomarkers TSG101 and CD81 were increased in peri-ischemic striatum after EA treatment, and we revealed 25 differentially expressed miRNAs in isolated exosomes, of which miR-146b was selected for further analysis, and demonstrated that EA increased miR-146b expression and its inhibitors could block the effects. Subsequently, we confirmed that EA upregulated miR-146b expression to promote neural stem cells differentiation into neurons in peri-ischemic striatum. In vitro, it was verified that OGD/R hindered neural stem cells differentiation, and miR-146b inhibitors furtherly suppressed its differentiation, simultaneously NeuroD1 was involved in neural stem cells differentiation into neurons. Moreover, in vivo we found EA promoted NeuroD1-mediated neural stem cells differentiation via miR-146b. In addition, EA also could improve neurological deficits through miR-146b after ischemic stroke.Conclusion: EA promotes the differentiation of endogenous neural stem cells via exosomal miR-146b to improve neurological injury after ischemic stroke.https://www.frontiersin.org/article/10.3389/fncel.2020.00223/fullelectro-acupunctureischemic strokeneural stem cellsexosomesMiR-146b
spellingShingle Shenghang Zhang
Shenghang Zhang
Tingting Jin
Lulu Wang
Weilin Liu
Yuhao Zhang
Yi Zheng
Yunjiao Lin
Minguang Yang
Xiaojun He
Huawei Lin
Lidian Chen
Jing Tao
Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke
Frontiers in Cellular Neuroscience
electro-acupuncture
ischemic stroke
neural stem cells
exosomes
MiR-146b
title Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke
title_full Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke
title_fullStr Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke
title_full_unstemmed Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke
title_short Electro-Acupuncture Promotes the Differentiation of Endogenous Neural Stem Cells via Exosomal microRNA 146b After Ischemic Stroke
title_sort electro acupuncture promotes the differentiation of endogenous neural stem cells via exosomal microrna 146b after ischemic stroke
topic electro-acupuncture
ischemic stroke
neural stem cells
exosomes
MiR-146b
url https://www.frontiersin.org/article/10.3389/fncel.2020.00223/full
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