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CX3CL1/CX3CR1 Axis Plays a Key Role in Ischemia-Induced Oligodendrocyte Injury via p38MAPK Signaling Pathway

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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.

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Abbreviations

CX3CL1:

Fractalkine

CX3CR1:

CX3CL1 receptor

IL-1β:

Interleukin-1β

OGD:

Oxygen and glucose deprivation

PLP:

Myelin proteolipid protein

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

The studies in our laboratories were supported by the General Grant of National Natural Science Foundation of China (NSFC) (81070930, 81471108, 31271132, 31371092), National 973 Programs (2011CB510004, 2014CB541604), the Competitive Earmarked Grants of The Hong Kong Research Grants Council (GRF 466713, 14106914), and Key Project Grant of NSFC (31330035). We thank Professor Peng Xie of the Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China for the human oligodendroglia cells.

Conflict of Interest

The authors declare that they have no competing interests.

Author Contributions

Y.L., Y. K., and Z.M.Q. conceived and supervised the study; X.M.W. and Q.Q.L. performed the experiments; Y.L. and X.M.W. contributed to the analysis of data. Y. K. and Z.M.Q. wrote the manuscript.

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Authors and Affiliations

  1. Department of Neurobiology, Institute for Nautical Medicine, Nantong University, Nantong, 226001, China

    Xiao-Mei Wu & Yong Liu

  2. Department of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400038, China

    Zhong-Ming Qian

  3. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

    Xiao-Mei Wu, Qian-Qian Luo & Ya Ke

  4. Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai, 201203, China

    Zhong-Ming Qian & Qian-Qian Luo

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  1. Xiao-Mei Wu
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Corresponding authors

Correspondence to Zhong-Ming Qian or Ya Ke.

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Xiao-Mei Wu and Yong Liu contributed equally to this work.

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Wu, XM., Liu, Y., Qian, ZM. et al. CX3CL1/CX3CR1 Axis Plays a Key Role in Ischemia-Induced Oligodendrocyte Injury via p38MAPK Signaling Pathway. Mol Neurobiol 53, 4010–4018 (2016). https://doi.org/10.1007/s12035-015-9339-3

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