Abstract
Oligodendrocytes (OLs) form myelin sheaths around axons in the central nervous system (CNS) facilitate the propagation of action potentials. The studies have shown that the differentiation and maturation of OLs involve microRNA (miR) regulation. The recent findings have addressed that miR-204 regulates OL differentiation in culture. In this study, through in situ hybridization in combination with immunohistochemistry, we showed that microRNA-204-5p in the corpus callosum was mainly expressed in OLs immunoreactive with adenomatous polyposis coli (APC), an OL marker. We also found miR-204-5p expression in mature OLs was suppressed by the addition of interleukin-6 (IL-6). Moreover, IL-6-induced inhibition of miR-204-5p expression was blocked by the addition of the inhibitors specific for p38 mitogen-activated protein kinase (p38MAPK) or phosphatidylinositol 3-kinase (PI3K) pathway. We further utilized a rat model by feeding cuprizone (CPZ)-containing diet for 3 weeks to induce demyelination and gliosis in the corpus callosum, as well as the upregulation of IL-6 gene expression significantly. Despite that miR-204-5p expression in the corpus callosum was not altered after feeding by CPZ for 3 weeks, its expression was increased and IL-6 transcription was decreased in the corpus callosum of the recovery group that was fed by CPZ for the first 2 weeks and by the regular diet for one more week. Our data demonstrate that miR-204-5p expression in OLs declined under the influence of the inflamed microenvironment. The findings that an increase in miR-204-5p and declined IL-6 expression observed in the recovery group might be involved with OL repair in the corpus callosum, and also shed light on a potential role for miR-204-5p in OL homeostasis following the white matter injury.
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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Abbreviations
- APC:
-
Adenomatous polyposis coli
- CNS:
-
Central nervous system
- CPZ:
-
Cuprizone
- CyPA:
-
Cyclophilin A
- DAB:
-
3,3′-Diaminobenzidine
- GC:
-
Galactocerebroside
- GFAP:
-
Glial fibrillary acidic protein
- HRP:
-
Horseradish peroxidase
- HS:
-
Horse serum
- Iba1:
-
Ionized calcium binding adaptor molecule 1
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- LFB:
-
Luxol fast blue
- miR:
-
MicroRNA
- MAPK:
-
Mitogen-activated protein kinase
- MS:
-
Multiple sclerosis
- MBP:
-
Myelin basic protein
- Myrf:
-
Myelin regulatory factor
- NSCs:
-
Neural stem cells
- OCT:
-
Optimal cutting temperature
- OLs:
-
Oligodendrocytes
- OPCs:
-
Oligodendrocyte precursor cells
- PFA:
-
Paraformaldehyde
- PBS:
-
Phosphate-buffered saline
- PI3K:
-
Phosphatidylinositol 3-kinase
- PLP:
-
Proteolipid protein
- QPCR:
-
Quantitative real time polymerase chain reaction
- RRID:
-
Research Resource Identifier (see scicrunch.org)
- Stat3:
-
Signal transducer and activator of transcription 3
- TNF-α:
-
Tumor necrosis factor-α
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Acknowledgements
The authors thank Ms. Ching-Ting Fu for technical assistance and the “Bio-image Core Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, Taiwan” for the technical services provided.
Funding
This study was supported by the Ministry of Science and Technology, Taiwan (MOST 109-2314-B006-015-MY3 and MOST 110-2811-B-006-522).
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HTH designed and implemented the experiments, and analyzed the data. CYW and CHH participated in the experimental work, and experimental technical support. SFT, the senior author, provided oversight, experimental design, result interpretation, and manuscript preparation/editing. All authors read and approved the final manuscript.
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Huang, HT., Wang, CY., Ho, CH. et al. Interleukin-6 Inhibits Expression of miR-204-5p, a Regulator of Oligodendrocyte Differentiation: Involvement of miR-204-5p in the Prevention of Chemical-Induced Oligodendrocyte Impairment. Mol Neurobiol 61, 1953–1968 (2024). https://doi.org/10.1007/s12035-023-03681-5
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DOI: https://doi.org/10.1007/s12035-023-03681-5