title: miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1.
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.
authors.affiliation: Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.|Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, 221009, China.
authors.forename: Sihan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Laboratory, No. 100 Hospital of CPLA, Suzhou, China.
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Ren
authors.affiliation: Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.
authors.forename: Xiuxiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Dong
authors.affiliation: Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.
authors.forename: Yadav Kaushal
authors.initials: YK
authors.lastname: Chand
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, 221009, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.
authors.forename: Ruiqin
authors.identifier: 0000-0001-7617-5438
authors.initials: R
authors.lastname: Yao
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, 221009, China.
authors.forename: Deqin
authors.initials: D
authors.lastname: Geng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology*; D003471:Cuprizone / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000235:genetics; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D013234:Stem Cells / Q000145:classification / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D003373:Coumaric Acids; D003471:Cuprizone; D035683:MicroRNAs; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C000609357:MIRN219 microRNA, mouse; C007175:alpha-cyano-4-hydroxycinnamate
keywords: demyelination; microRNA; monocarboxylate transporter 1; oligodendrocyte; remyelination