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Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

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Abstract

Aspirin, one of the most commonly used anti-inflammatory drugs, has been recently reported to display multiple effects in the central nervous system (CNS), including neuroprotection and upregulation of ciliary neurotrophic factor (CNTF) expression in astrocytes. Although it was most recently reported that aspirin could promote the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) after white matter lesion, the underlying mechanisms remain unclear. To dissect the effects of aspirin on oligodendroglial development and explore possible mechanisms, we here demonstrated the following: (i) in vitro treatment of aspirin on OPC cultures significantly increased the number of differentiated oligodendrocytes (OLs) but had no effect on the number of proliferative OPCs, indicating that aspirin can promote OPC differentiation but not proliferation; (ii) in vivo treatment of aspirin on neonatal (P3) rats for 4 days led to a nearly twofold increase in the expression of myelin basic protein (MBP), devoid of change in OPC proliferaion, in the corpus callosum (CC); (iii) finally, aspirin treatment increased the phosphorylation level of β-catenin and counteracted Wnt signaling pathway synergist QS11-induced suppression on OPC differentiation. Together, our data show that aspirin can directly target oligodendroglial lineage cells and promote their differentiation through inhibition of Wnt/β-catenin signaling pathway. These findings suggest that aspirin may be a novel candidate for the treatment of demyelinating diseases.

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Acknowledgments

This work is supported by the National Natural Science Foundation of China (NSCF 31171046, 31300906) and the Natural Science Foundation Project of Chongqing (CSTC2013jcyjA10100).

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Authors and Affiliations

  1. Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China

    Nanxin Huang, Dong Chen, Xiyan Wu, Xianjun Chen, Xuesi Zhang, Jianqin Niu & Lan Xiao

  2. Department of Biological Technique, Third Military Medical University, Chongqing, 400038, China

    Dong Chen

  3. Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR, 97232, USA

    Hai-Ying Shen

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  1. Nanxin Huang
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  2. Dong Chen
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Correspondence to Jianqin Niu or Lan Xiao.

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Huang, N., Chen, D., Wu, X. et al. Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway. Mol Neurobiol 53, 3258–3266 (2016). https://doi.org/10.1007/s12035-015-9241-z

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  • DOI: https://doi.org/10.1007/s12035-015-9241-z

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