Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion

Myelin is closely associated with cognitive function and is extremely vulnerable to damage in ischemic cerebrovascular diseases. The failure of remyelination is mainly due to limitations in oligodendrocyte progenitor cells (OPCs) differentiation in the damaged area. Previous studies have shown that...

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Main Authors: Ting Jiang, Liying Zhang, Xiaona Pan, Haiqing Zheng, Xi Chen, Lili Li, Jing Luo, Xiquan Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-12-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fncel.2017.00404/full
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author Ting Jiang
Liying Zhang
Xiaona Pan
Haiqing Zheng
Xi Chen
Lili Li
Jing Luo
Xiquan Hu
author_facet Ting Jiang
Liying Zhang
Xiaona Pan
Haiqing Zheng
Xi Chen
Lili Li
Jing Luo
Xiquan Hu
author_sort Ting Jiang
collection DOAJ
description Myelin is closely associated with cognitive function and is extremely vulnerable to damage in ischemic cerebrovascular diseases. The failure of remyelination is mainly due to limitations in oligodendrocyte progenitor cells (OPCs) differentiation in the damaged area. Previous studies have shown that physical exercise can improve vascular cognitive impairment, but whether it can reverse the defect in remyelination during ischemic injury and the underlying mechanism remains unclear. In this study, we observed the effects of physical exercise on chronic cerebral hypoperfusion (CCH) established by bilateral carotid artery occlusion. The cognitive function, myelin integrity, OPCs proliferation and differentiation, as well as microglia polarization were analyzed at 28 days after CCH. Besides, the expression of CX3CL1/CX3CR1 axis and activation of mitogen-activated protein kinase (MAPK) signal cascades were also evaluated. We found that physical exercise improved the cognitive function of rats with CCH, alleviated myelin injury, triggered OPCs proliferation and differentiation, facilitated microglia polarization toward M2, augmented the expression of CX3CL1/CX3CR1 axis, and reduced ERK and JNK phosphorylation. The results indicated that physical exercise improved the cognitive function of rats with CCH, possibly through microglial phenotype modulation and enhancement of oligodendrocytegenesis and remyelination. Moreover, the CX3CL1/CX3CR1 axis played an important role in this process by mediating ERK- and JNK-dependent pathways.
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spelling doaj.art-8b3cdd306b87474b8c373270807b37852022-12-22T00:57:11ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-12-011110.3389/fncel.2017.00404288870Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral HypoperfusionTing Jiang0Liying Zhang1Xiaona Pan2Haiqing Zheng3Xi Chen4Lili Li5Jing Luo6Xiquan Hu7epartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Chinaepartment of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaMyelin is closely associated with cognitive function and is extremely vulnerable to damage in ischemic cerebrovascular diseases. The failure of remyelination is mainly due to limitations in oligodendrocyte progenitor cells (OPCs) differentiation in the damaged area. Previous studies have shown that physical exercise can improve vascular cognitive impairment, but whether it can reverse the defect in remyelination during ischemic injury and the underlying mechanism remains unclear. In this study, we observed the effects of physical exercise on chronic cerebral hypoperfusion (CCH) established by bilateral carotid artery occlusion. The cognitive function, myelin integrity, OPCs proliferation and differentiation, as well as microglia polarization were analyzed at 28 days after CCH. Besides, the expression of CX3CL1/CX3CR1 axis and activation of mitogen-activated protein kinase (MAPK) signal cascades were also evaluated. We found that physical exercise improved the cognitive function of rats with CCH, alleviated myelin injury, triggered OPCs proliferation and differentiation, facilitated microglia polarization toward M2, augmented the expression of CX3CL1/CX3CR1 axis, and reduced ERK and JNK phosphorylation. The results indicated that physical exercise improved the cognitive function of rats with CCH, possibly through microglial phenotype modulation and enhancement of oligodendrocytegenesis and remyelination. Moreover, the CX3CL1/CX3CR1 axis played an important role in this process by mediating ERK- and JNK-dependent pathways.http://journal.frontiersin.org/article/10.3389/fncel.2017.00404/fullphysical exercisevascular cognitive impairmentremyelinationM2 microgliaCX3CL1/CX3CR1 axis
spellingShingle Ting Jiang
Liying Zhang
Xiaona Pan
Haiqing Zheng
Xi Chen
Lili Li
Jing Luo
Xiquan Hu
Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion
Frontiers in Cellular Neuroscience
physical exercise
vascular cognitive impairment
remyelination
M2 microglia
CX3CL1/CX3CR1 axis
title Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion
title_full Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion
title_fullStr Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion
title_full_unstemmed Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion
title_short Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion
title_sort physical exercise improves cognitive function together with microglia phenotype modulation and remyelination in chronic cerebral hypoperfusion
topic physical exercise
vascular cognitive impairment
remyelination
M2 microglia
CX3CL1/CX3CR1 axis
url http://journal.frontiersin.org/article/10.3389/fncel.2017.00404/full
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