PMID- 27873367 OWN - NLM STAT- MEDLINE DCOM- 20180206 LR - 20180619 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 45 IP - 2 DP - 2017 Jan TI - miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1. PG - 249-259 LID - 10.1111/ejn.13485 [doi] AB - 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 alpha-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. CI - (c) 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Liu, Sihan AU - Liu S AD - Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China. AD - Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, 221009, China. FAU - Ren, Chuanlu AU - Ren C AD - Department of Laboratory, No. 100 Hospital of CPLA, Suzhou, China. FAU - Qu, Xuebin AU - Qu X AD - Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China. FAU - Wu, Xiuxiang AU - Wu X AD - Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China. FAU - Dong, Fuxing AU - Dong F AD - Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China. FAU - Chand, Yadav Kaushal AU - Chand YK AD - Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China. FAU - Fan, Hongbin AU - Fan H AD - Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, 221009, China. FAU - Yao, Ruiqin AU - Yao R AUID- ORCID: 0000-0001-7617-5438 AD - Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China. FAU - Geng, Deqin AU - Geng D AD - Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, 221009, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Coumaric Acids) RN - 0 (MIRN219 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Monocarboxylic Acid Transporters) RN - 0 (Symporters) RN - 0 (monocarboxylate transport protein 1) RN - 28166-41-8 (alpha-cyano-4-hydroxycinnamate) RN - 5N16U7E0AO (Cuprizone) SB - IM MH - Animals MH - Cell Differentiation/drug effects/physiology MH - Cell Proliferation/physiology MH - Cells, Cultured MH - Corpus Callosum/metabolism MH - Coumaric Acids/*pharmacology MH - Cuprizone/*pharmacology MH - Demyelinating Diseases/*drug therapy/genetics MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics MH - Monocarboxylic Acid Transporters/*metabolism MH - Myelin Sheath/drug effects/metabolism MH - Oligodendroglia/*drug effects/metabolism MH - Stem Cells/classification/metabolism MH - Symporters/*metabolism OTO - NOTNLM OT - demyelination OT - microRNA OT - monocarboxylate transporter 1 OT - oligodendrocyte OT - remyelination EDAT- 2016/11/23 06:00 MHDA- 2018/02/07 06:00 CRDT- 2016/11/23 06:00 PHST- 2016/09/11 00:00 [received] PHST- 2016/11/17 00:00 [revised] PHST- 2016/11/18 00:00 [accepted] PHST- 2016/11/23 06:00 [pubmed] PHST- 2018/02/07 06:00 [medline] PHST- 2016/11/23 06:00 [entrez] AID - 10.1111/ejn.13485 [doi] PST - ppublish SO - Eur J Neurosci. 2017 Jan;45(2):249-259. doi: 10.1111/ejn.13485.