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Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage

White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been re...

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Autores principales: Xin, Yuanjun, Chen, Jie, Zhang, Hongxia, Ostrowski, Robert P., Liang, Yidan, Zhao, Jun, Xiang, Xiang, Liang, Fuming, Fu, Wenqiao, Huang, Hao, Wu, Xintong, Su, Jun, Deng, Jiewen, He, Zhaohui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9564295/
https://www.ncbi.nlm.nih.gov/pubmed/36230939
http://dx.doi.org/10.3390/cells11192976
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author Xin, Yuanjun
Chen, Jie
Zhang, Hongxia
Ostrowski, Robert P.
Liang, Yidan
Zhao, Jun
Xiang, Xiang
Liang, Fuming
Fu, Wenqiao
Huang, Hao
Wu, Xintong
Su, Jun
Deng, Jiewen
He, Zhaohui
author_facet Xin, Yuanjun
Chen, Jie
Zhang, Hongxia
Ostrowski, Robert P.
Liang, Yidan
Zhao, Jun
Xiang, Xiang
Liang, Fuming
Fu, Wenqiao
Huang, Hao
Wu, Xintong
Su, Jun
Deng, Jiewen
He, Zhaohui
author_sort Xin, Yuanjun
collection PubMed
description White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH.
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spelling pubmed-95642952022-10-15 Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage Xin, Yuanjun Chen, Jie Zhang, Hongxia Ostrowski, Robert P. Liang, Yidan Zhao, Jun Xiang, Xiang Liang, Fuming Fu, Wenqiao Huang, Hao Wu, Xintong Su, Jun Deng, Jiewen He, Zhaohui Cells Article White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH. MDPI 2022-09-24 /pmc/articles/PMC9564295/ /pubmed/36230939 http://dx.doi.org/10.3390/cells11192976 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xin, Yuanjun
Chen, Jie
Zhang, Hongxia
Ostrowski, Robert P.
Liang, Yidan
Zhao, Jun
Xiang, Xiang
Liang, Fuming
Fu, Wenqiao
Huang, Hao
Wu, Xintong
Su, Jun
Deng, Jiewen
He, Zhaohui
Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
title Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
title_full Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
title_fullStr Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
title_full_unstemmed Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
title_short Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
title_sort dexras1 induces dysdifferentiation of oligodendrocytes and myelin injury by inhibiting the camp-creb pathway after subarachnoid hemorrhage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9564295/
https://www.ncbi.nlm.nih.gov/pubmed/36230939
http://dx.doi.org/10.3390/cells11192976
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