期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 45, 期 2, 页码 249-259出版社
WILEY
DOI: 10.1111/ejn.13485
关键词
demyelination; microRNA; monocarboxylate transporter 1; oligodendrocyte; remyelination
资金
- National Natural Science Foundation of China (NSFC) [81271345, 81302519]
- Natural Science Foundation of Jiangsu Province [BK20131132, BK20130221, BK20161174]
- Qing Lan Project of Jiangsu Province
- University Science Research Project of Jiangsu Province [15KJB180018, 15KJB310023]
Remyelination is limited in patients with multiple sclerosis (MS) due to the difficulties in recruiting proliferating oligodendrocyte precursors (OPCs), the inhibition of OPC differentiation and/or maturation, and/or failure in the generation of the myelin sheath. In vitro studies have revealed that miR-219 is necessary for OPC differentiation and monocarboxylate transporter 1 (MCT1) plays a vital role in oligodendrocyte maturation and myelin synthesis. Herein, we hypothesized that miR-219 might promote oligodendrocyte differentiation and attenuate demyelination in a cuprizone (CPZ)-induced demyelinated model by regulating the expression of MCT1. We found that CPZ-treated mice exhibited significantly increased anxiety in the open field test. However, miR-219 reduced anxiety as shown by an increase in the total distance, the central distance and the mean amount of time spent in the central area. miR-219 decreased the quantity of OPCs and increased the number of oligodendrocytes and the level of myelin basic protein (MBP) and cyclic nucleotide 3 phosphodiesterase (CNP) protein. Ultrastructural studies further confirmed that the extent of demyelination was attenuated by miR-219 overexpression. Meanwhile, miR-219 also greatly enhanced MCT1 expression via suppression of oligodendrocyte differentiation inhibitors, Sox6 and Hes5, treatment with the MCT1 inhibitor -cyano-4-hydroxycinnamate (4-CIN) reduced the number of oligodendrocytes and the protein levels of MBP and CNP. Taken together, these results suggest a novel mode of action of miR-219 via MCT1 invivo and may provide a new potential remyelination therapeutic target.
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