title: Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway.
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.
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Nanxin
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.|Department of Biological Technique, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China. jianqinniu@163.com.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Niu
authors.affiliation: Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR, 97232, USA.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Shen
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China. xiaolan35@tmmu.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D003337:Corpus Callosum / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D020934:Ciliary Neurotrophic Factor; D051176:beta Catenin; D001241:Aspirin
keywords: Aspirin; Differentiation; Oligodendrocyte; Oligodendrocyte precursor cell; Wnt/β-catenin