Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ
Preterm white matter injury (PWMI), characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination, is a prevalent demyelinating disease of the central nervous system in premature infants, necessitating the development of mitigating strategies. Convincing evidence...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223006054 |
| _version_ | 1797822157657473024 |
|---|---|
| author | Zhaowei Feng Zixuan Gao Renyu Kong Tao Zhuang Jing Liu Ting Liu Xiaohui Zheng Yajun Bai Ruiqin Yao |
| author_facet | Zhaowei Feng Zixuan Gao Renyu Kong Tao Zhuang Jing Liu Ting Liu Xiaohui Zheng Yajun Bai Ruiqin Yao |
| author_sort | Zhaowei Feng |
| collection | DOAJ |
| description | Preterm white matter injury (PWMI), characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination, is a prevalent demyelinating disease of the central nervous system in premature infants, necessitating the development of mitigating strategies. Convincing evidence suggests that peroxisome proliferator-activated receptor γ (PPARγ) activation is a stimulative factor against the hindered process of oligodendrocyte (OL) differentiation. However, much remains unknown about its promotive mechanism. Our previous study indicated that alpha-asaronol (α-asaronol) could alleviate myelination disorder in a neonatal PWMI rat model, but the mechanism remained unclear. In this study, we demonstrated that α-asaronol attenuated cognitive deficits, repaired myelin damage, and stimulated OL differentiation in the corpus callosum of PWMI rats. Co-immunoprecipitation analysis confirmed that α-asaronol induced the binding of PPARγ with its coactivator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which in turn activated oligodendroglial PPARγ. This activation subsequently upregulated the expression of phosphatase and tensin homolog (PTEN) and pro-differentiation-associated genes of Cnp1 and Klk6 and downregulated the expression of Clk1. However, the benefits of α-asaronol were blocked by GW9662, an antagonist of PPARγ. Moreover, α-asaronol also promoted OPC differentiation under oxygen-glucose deprivation conditions. In conclusion, α-asaronol can promote OL differentiation and myelination and alleviate cognitive deficits in neonatal PWMI rats by activating PPARγ and modulating OL differentiation-associated gene expression. This study suggests that α-asaronol may be a potential therapeutic drug for myelination failure in PWMI. |
| first_indexed | 2024-03-13T10:03:43Z |
| format | Article |
| id | doaj.art-e5f30f3836a4489a937394058d112d60 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-13T10:03:43Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-e5f30f3836a4489a937394058d112d602023-05-23T04:21:10ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-07-01163114815Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγZhaowei Feng0Zixuan Gao1Renyu Kong2Tao Zhuang3Jing Liu4Ting Liu5Xiaohui Zheng6Yajun Bai7Ruiqin Yao8Department of Neurology, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, ChinaDepartment of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, ChinaDepartment of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, ChinaDepartment of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, ChinaDepartment of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, ChinaNursing Department, Xuzhou Pharmaceutical Branch of Jiangsu Union Technical Institute, Xuzhou, Jiangsu Province, ChinaKey Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, ChinaKey Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, China; Corresponding authors.Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Corresponding authors.Preterm white matter injury (PWMI), characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination, is a prevalent demyelinating disease of the central nervous system in premature infants, necessitating the development of mitigating strategies. Convincing evidence suggests that peroxisome proliferator-activated receptor γ (PPARγ) activation is a stimulative factor against the hindered process of oligodendrocyte (OL) differentiation. However, much remains unknown about its promotive mechanism. Our previous study indicated that alpha-asaronol (α-asaronol) could alleviate myelination disorder in a neonatal PWMI rat model, but the mechanism remained unclear. In this study, we demonstrated that α-asaronol attenuated cognitive deficits, repaired myelin damage, and stimulated OL differentiation in the corpus callosum of PWMI rats. Co-immunoprecipitation analysis confirmed that α-asaronol induced the binding of PPARγ with its coactivator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which in turn activated oligodendroglial PPARγ. This activation subsequently upregulated the expression of phosphatase and tensin homolog (PTEN) and pro-differentiation-associated genes of Cnp1 and Klk6 and downregulated the expression of Clk1. However, the benefits of α-asaronol were blocked by GW9662, an antagonist of PPARγ. Moreover, α-asaronol also promoted OPC differentiation under oxygen-glucose deprivation conditions. In conclusion, α-asaronol can promote OL differentiation and myelination and alleviate cognitive deficits in neonatal PWMI rats by activating PPARγ and modulating OL differentiation-associated gene expression. This study suggests that α-asaronol may be a potential therapeutic drug for myelination failure in PWMI.http://www.sciencedirect.com/science/article/pii/S0753332223006054White matter injuryoligodendrocyte precursor cellPPARγDifferentiationalpha-asaronol |
| spellingShingle | Zhaowei Feng Zixuan Gao Renyu Kong Tao Zhuang Jing Liu Ting Liu Xiaohui Zheng Yajun Bai Ruiqin Yao Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ Biomedicine & Pharmacotherapy White matter injury oligodendrocyte precursor cell PPARγ Differentiation alpha-asaronol |
| title | Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ |
| title_full | Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ |
| title_fullStr | Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ |
| title_full_unstemmed | Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ |
| title_short | Alpha-asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator PPARγ |
| title_sort | alpha asaronol promoted oligodendrocyte precursor cell differentiation and improved myelination as an activator pparγ |
| topic | White matter injury oligodendrocyte precursor cell PPARγ Differentiation alpha-asaronol |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223006054 |
| work_keys_str_mv | AT zhaoweifeng alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT zixuangao alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT renyukong alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT taozhuang alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT jingliu alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT tingliu alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT xiaohuizheng alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT yajunbai alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg AT ruiqinyao alphaasaronolpromotedoligodendrocyteprecursorcelldifferentiationandimprovedmyelinationasanactivatorpparg |