MiR‐219 attenuates demyelination in cuprizone‐induced demyelinated mice by regulating monocarboxylate transporter 1. (January 2017)

• Record Type: Journal Article
• Authors: Liu, Sihan; Ren, Chuanlu; Qu, Xuebin; Wu, Xiuxiang; Dong, Fuxing; Chand, Yadav Kaushal; Fan, Hongbin; Yao, Ruiqin; Geng, Deqin
• Editors: Majewska, Ania
• Is Part Of: European journal of neuroscience. Volume 45:Number 2(2017)
• Page Start: 249
• Page End: 259
• Publication Date: 2017-01
• Subjects: demyelination -- microRNA -- monocarboxylate transporter 1 -- oligodendrocyte -- remyelination; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13485
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: 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 α‐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 in vivo and may provide a new potential remyelination therapeutic target. Abstract : miR‐219 promoted oligodendrocyte differentiation, alleviated demyelination, decreased anxiety‐like behaviors and increased exploratory behavior ability in CPZ‐induced demyelinated mice. We also confirmed that MCT1 is necessary for oligodendrocyte differentiation and survival. Further, MCT1 might be involved in the effects of miR‐219 on oligodendrocyte differentiation and remyelination.