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Updated: Mar 11, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1
Sihan Liu1,2, Chuanlu Ren3, Xuebin Qu1
1Research Center for Neurobiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, China.
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.
Insights
MicroRNA-219 (miR-219) promotes oligodendrocyte differentiation and remyelination in a mouse model of multiple sclerosis by enhancing monocarboxylate transporter 1 (MCT1) expression. This finding suggests miR-219 as a potential therapeutic target for promoting myelin repair.
Area of Science:
- Neuroscience
- Molecular Biology
- Demyelinating Diseases
Background:
- Remyelination in multiple sclerosis (MS) is hindered by issues with oligodendrocyte precursor cell (OPC) recruitment, differentiation, and myelin sheath formation.
- In vitro studies highlight miR-219's role in OPC differentiation and monocarboxylate transporter 1 (MCT1)'s importance in oligodendrocyte maturation and myelin synthesis.
Purpose of the Study:
- To investigate the potential of miR-219 to promote oligodendrocyte differentiation and reduce demyelination in a cuprizone-induced mouse model.
- To explore whether miR-219 exerts its effects by regulating MCT1 expression.
Main Methods:
- Utilized a cuprizone (CPZ)-induced demyelination mouse model.
- Assessed anxiety-like behavior using the open field test.
- Quantified oligodendrocyte precursor cells (OPCs), oligodendrocytes, myelin basic protein (MBP), and cyclic nucleotide 3' phosphodiesterase (CNP) levels.
- Performed ultrastructural studies to evaluate demyelination.
- Investigated the effect of MCT1 inhibition using α-cyano-4-hydroxycinnamate (4-CIN).
Main Results:
- CPZ-induced demyelination was associated with increased anxiety, which was reduced by miR-219.
- miR-219 decreased OPCs, increased oligodendrocytes, and elevated MBP and CNP protein levels.
- miR-219 overexpression attenuated demyelination, enhanced MCT1 expression by suppressing Sox6 and Hes5, and MCT1 inhibition reversed these beneficial effects.
Conclusions:
- miR-219 promotes oligodendrocyte differentiation and myelin repair in vivo, partly through MCT1 regulation.
- miR-219 may offer a novel therapeutic strategy for remyelination in demyelinating diseases like MS.
