Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway
Autor: | Dong Chen, Xianjun Chen, Lan Xiao, Xiyan Wu, Hai-Ying Shen, Nanxin Huang, Jianqin Niu, Xuesi Zhang |
---|---|
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Neuroscience (miscellaneous) Biology Ciliary neurotrophic factor Neuroprotection Corpus Callosum Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation medicine Animals Ciliary Neurotrophic Factor Phosphorylation Wnt Signaling Pathway Cells Cultured beta Catenin Cell Proliferation Aspirin Wnt signaling pathway Cell Differentiation Oligodendrocyte Myelin basic protein Oligodendroglia 030104 developmental biology medicine.anatomical_structure Neurology Immunology Cancer research biology.protein Signal transduction 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Molecular Neurobiology. 53:3258-3266 |
ISSN: | 1559-1182 0893-7648 |
DOI: | 10.1007/s12035-015-9241-z |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |