Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System
Several microRNAs (miRNAs), including miR-23 and miR-27a have been reportedly involved in regulating myelination in the central nervous system. Although miR-23 and miR-27a form clusters in vivo and the clustered miRNAs are known to perform complementary functions, the role of these miRNA clusters in...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2023/8938674 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832547833774866432 |
|---|---|
| author | Yuji Tsuchikawa Naosuke Kamei Yohei Sanada Toshio Nakamae Takahiro Harada Kazunori Imaizumi Takayuki Akimoto Shigeru Miyaki Nobuo Adachi |
| author_facet | Yuji Tsuchikawa Naosuke Kamei Yohei Sanada Toshio Nakamae Takahiro Harada Kazunori Imaizumi Takayuki Akimoto Shigeru Miyaki Nobuo Adachi |
| author_sort | Yuji Tsuchikawa |
| collection | DOAJ |
| description | Several microRNAs (miRNAs), including miR-23 and miR-27a have been reportedly involved in regulating myelination in the central nervous system. Although miR-23 and miR-27a form clusters in vivo and the clustered miRNAs are known to perform complementary functions, the role of these miRNA clusters in myelination has not been studied. To investigate the role of miR-23-27-24 clusters in myelination, we generated miR-23-27-24 cluster knockout mice and evaluated myelination in the brain and spinal cord. Our results showed that 10-week-old knockout mice had reduced motor function in the hanging wire test compared to the wild-type mice. At 4 weeks, 10 weeks, and 12 months of age, knockout mice showed reduced myelination compared to wild-type mice. The expression levels of myelin basic protein and myelin proteolipid protein were also significantly lower in the knockout mice compared to the wild-type mice. Although differentiation of oligodendrocyte progenitor cells to oligodendrocytes was not inhibited in the knockout mice, the percentage of oligodendrocytes expressing myelin basic protein was significantly lower in 4-week-old knockout mice than that in wild-type mice. Proteome analysis and western blotting showed increased expression of leucine-zipper-like transcription regulator 1 (LZTR1) and decreased expression of R-RAS and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in the knockout mice. In summary, loss of miR-23-27-24 clusters reduces myelination and compromises motor functions in mice. Further, LZTR1, which regulates R-RAS upstream of the ERK1/2 pathway, a signal that promotes myelination, has been identified as a novel target of the miR-23-27-24 cluster in this study. |
| format | Article |
| id | doaj-art-38605a65d28840bead0c570769ec147f |
| institution | Kabale University |
| issn | 1687-5443 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-38605a65d28840bead0c570769ec147f2025-02-03T06:43:13ZengWileyNeural Plasticity1687-54432023-01-01202310.1155/2023/8938674Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous SystemYuji Tsuchikawa0Naosuke Kamei1Yohei Sanada2Toshio Nakamae3Takahiro Harada4Kazunori Imaizumi5Takayuki Akimoto6Shigeru Miyaki7Nobuo Adachi8Department of Orthopaedic SurgeryDepartment of Orthopaedic SurgeryDepartment of Orthopaedic SurgeryDepartment of Orthopaedic SurgeryDepartment of Orthopaedic SurgeryDepartment of BiochemistryFaculty of Sport SciencesDepartment of Orthopaedic SurgeryDepartment of Orthopaedic SurgerySeveral microRNAs (miRNAs), including miR-23 and miR-27a have been reportedly involved in regulating myelination in the central nervous system. Although miR-23 and miR-27a form clusters in vivo and the clustered miRNAs are known to perform complementary functions, the role of these miRNA clusters in myelination has not been studied. To investigate the role of miR-23-27-24 clusters in myelination, we generated miR-23-27-24 cluster knockout mice and evaluated myelination in the brain and spinal cord. Our results showed that 10-week-old knockout mice had reduced motor function in the hanging wire test compared to the wild-type mice. At 4 weeks, 10 weeks, and 12 months of age, knockout mice showed reduced myelination compared to wild-type mice. The expression levels of myelin basic protein and myelin proteolipid protein were also significantly lower in the knockout mice compared to the wild-type mice. Although differentiation of oligodendrocyte progenitor cells to oligodendrocytes was not inhibited in the knockout mice, the percentage of oligodendrocytes expressing myelin basic protein was significantly lower in 4-week-old knockout mice than that in wild-type mice. Proteome analysis and western blotting showed increased expression of leucine-zipper-like transcription regulator 1 (LZTR1) and decreased expression of R-RAS and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in the knockout mice. In summary, loss of miR-23-27-24 clusters reduces myelination and compromises motor functions in mice. Further, LZTR1, which regulates R-RAS upstream of the ERK1/2 pathway, a signal that promotes myelination, has been identified as a novel target of the miR-23-27-24 cluster in this study.http://dx.doi.org/10.1155/2023/8938674 |
| spellingShingle | Yuji Tsuchikawa Naosuke Kamei Yohei Sanada Toshio Nakamae Takahiro Harada Kazunori Imaizumi Takayuki Akimoto Shigeru Miyaki Nobuo Adachi Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System Neural Plasticity |
| title | Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System |
| title_full | Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System |
| title_fullStr | Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System |
| title_full_unstemmed | Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System |
| title_short | Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System |
| title_sort | deficiency of microrna 23 27 24 clusters exhibits the impairment of myelination in the central nervous system |
| url | http://dx.doi.org/10.1155/2023/8938674 |
| work_keys_str_mv | AT yujitsuchikawa deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT naosukekamei deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT yoheisanada deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT toshionakamae deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT takahiroharada deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT kazunoriimaizumi deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT takayukiakimoto deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT shigerumiyaki deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem AT nobuoadachi deficiencyofmicrorna232724clustersexhibitstheimpairmentofmyelinationinthecentralnervoussystem |