title: CX3CL1/CX3CR1 Axis Plays a Key Role in Ischemia-Induced Oligodendrocyte Injury via p38MAPK Signaling Pathway.
abstract: Based on current knowledge on the role of the CX3CL1/CX3CR1 axis in the regulation of microglial activation and on the involvement of activated microglia in damaging oligodendrocytes, we hypothesized that CX3CL1/CX3CR1 axis is associated with the development of ischemic oligodendrocyte and white matter injury. We investigated the effects of CX3CL1, CX3CR1 shRNA, and p38MAPK inhibitor on the apoptosis, proliferation, and myelin proteolipid protein (PLP) expression in oligodendrocytes in co-cultures with BV2 microglia under ischemia. We demonstrated that CX3CL1 markedly increased the numbers of apoptotic oligodendrocytes, decreased PLP expression in oligodendrocytes, and inhibited the increased proliferation of oligodendrocytes induced by ischemia in co-cultures. All these effects of CX3CL1 were suppressed by pre-treatment of BV2 microglia with CX3CR1 shRNA to silence CX3CR1 expression or SB203580 to inhibit p38MAPK pathway. Our findings support that CX3CL1/CX3CR1 axis plays a key role in the development of ischemia-induced oligodendrocyte injury via p38MAPK signaling pathway.
authors.affiliation: Department of Neurobiology, Institute for Nautical Medicine, Nantong University, Nantong, 226001, China.|School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Department of Neurobiology, Institute for Nautical Medicine, Nantong University, Nantong, 226001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400038, China. qianzhongming@fudan.edu.cn.|Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai, 201203, China. qianzhongming@fudan.edu.cn.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Qian
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.|Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai, 201203, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Luo
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. yake@cuhk.edu.hk.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D017209:Apoptosis; D000073883:CX3C Chemokine Receptor 1 / Q000378:metabolism*; D049109:Cell Proliferation; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D018920:Coculture Techniques; D005947:Glucose / Q000172:deficiency; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007511:Ischemia / Q000473:pathology*; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology*; D010100:Oxygen; D010766:Phosphorylation; D011510:Proteolipids / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D053583:Interleukin-1beta; D011510:Proteolipids; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen
keywords: BV2 microglia; CX3CL1/CX3CR1 axis; Ischemia; Microglial activation; Oligodendrocyte; p38MAPK pathway