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PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats
In early brain injury (EBI) after subarachnoid hemorrhage (SAH), white matter (WM) axonal injury plays a key role in the prognosis of the disease. The purpose of this study was to investigate the effects of phosphatase and tensin homolog deleted on chromosome ten (PTEN) on axonal injury and neuronal...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Chongqing Medical University
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720672/ https://www.ncbi.nlm.nih.gov/pubmed/35005122 http://dx.doi.org/10.1016/j.gendis.2020.05.002 |
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author | Chen, Hong Zhou, Chao Zheng, Jianfeng Zhang, Zhaosi Deng, Yongbing Cheng, Chongjie Guo, Zongduo Huo, Gang Yin, Cheng Sun, Xiaochuan |
author_facet | Chen, Hong Zhou, Chao Zheng, Jianfeng Zhang, Zhaosi Deng, Yongbing Cheng, Chongjie Guo, Zongduo Huo, Gang Yin, Cheng Sun, Xiaochuan |
author_sort | Chen, Hong |
collection | PubMed |
description | In early brain injury (EBI) after subarachnoid hemorrhage (SAH), white matter (WM) axonal injury plays a key role in the prognosis of the disease. The purpose of this study was to investigate the effects of phosphatase and tensin homolog deleted on chromosome ten (PTEN) on axonal injury and neuronal apoptosis post-SAH in rats and to find its underlying mechanism. Adeno-associated virus was injected into the lateral ventricle to suppress or promote PTEN. Neural function post-SAH in animals was determined by the modified Garcia score, beam balance, and Rotarod test, and the blood–brain barrier disruption was assessed by the brain water content. Axonal injury post-SAH was observed by TEM and determined by IF, and neuron apoptosis was measured by TUNEL staining. The mechanism was analyzed by Western blot to detect p-PTEN/PTEN, p-AKT/AKT, p-GSK-3β/GSK-3β, p-CRMP-2/CRMP-2, axonal injury marker β-APP and pro- and anti-apoptosis proteins, including Bax and Bcl-2, expression. We found 1. After knocking down PTEN, neuronal apoptosis and axonal injury were alleviated, and nerve function and blood–brain barrier were protected; accordingly, after overexpression of PTEN, neuronal apoptosis and axon damage were aggravated, and nerve function damage and blood–brain barrier damage were increased. 2. PTEN and AKT/GSK-3β/CRMP-2 pathway were jointly involved in regulating neuronal apoptosis and WM axon injury after SAH. According to our research, PTEN was a negative factor of EBI, and together with the AKT/GSK-3β/CRMP-2 signaling pathway aggravates neuronal apoptosis and WM axon damage after SAH. Inhibition of PTEN expression may become a new target for SAH treatment. |
format | Online Article Text |
id | pubmed-8720672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Chongqing Medical University |
record_format | MEDLINE/PubMed |
spelling | pubmed-87206722022-01-07 PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats Chen, Hong Zhou, Chao Zheng, Jianfeng Zhang, Zhaosi Deng, Yongbing Cheng, Chongjie Guo, Zongduo Huo, Gang Yin, Cheng Sun, Xiaochuan Genes Dis Full Length Article In early brain injury (EBI) after subarachnoid hemorrhage (SAH), white matter (WM) axonal injury plays a key role in the prognosis of the disease. The purpose of this study was to investigate the effects of phosphatase and tensin homolog deleted on chromosome ten (PTEN) on axonal injury and neuronal apoptosis post-SAH in rats and to find its underlying mechanism. Adeno-associated virus was injected into the lateral ventricle to suppress or promote PTEN. Neural function post-SAH in animals was determined by the modified Garcia score, beam balance, and Rotarod test, and the blood–brain barrier disruption was assessed by the brain water content. Axonal injury post-SAH was observed by TEM and determined by IF, and neuron apoptosis was measured by TUNEL staining. The mechanism was analyzed by Western blot to detect p-PTEN/PTEN, p-AKT/AKT, p-GSK-3β/GSK-3β, p-CRMP-2/CRMP-2, axonal injury marker β-APP and pro- and anti-apoptosis proteins, including Bax and Bcl-2, expression. We found 1. After knocking down PTEN, neuronal apoptosis and axonal injury were alleviated, and nerve function and blood–brain barrier were protected; accordingly, after overexpression of PTEN, neuronal apoptosis and axon damage were aggravated, and nerve function damage and blood–brain barrier damage were increased. 2. PTEN and AKT/GSK-3β/CRMP-2 pathway were jointly involved in regulating neuronal apoptosis and WM axon injury after SAH. According to our research, PTEN was a negative factor of EBI, and together with the AKT/GSK-3β/CRMP-2 signaling pathway aggravates neuronal apoptosis and WM axon damage after SAH. Inhibition of PTEN expression may become a new target for SAH treatment. Chongqing Medical University 2020-06-18 /pmc/articles/PMC8720672/ /pubmed/35005122 http://dx.doi.org/10.1016/j.gendis.2020.05.002 Text en © 2020 Chongqing Medical University. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Full Length Article Chen, Hong Zhou, Chao Zheng, Jianfeng Zhang, Zhaosi Deng, Yongbing Cheng, Chongjie Guo, Zongduo Huo, Gang Yin, Cheng Sun, Xiaochuan PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats |
title | PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats |
title_full | PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats |
title_fullStr | PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats |
title_full_unstemmed | PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats |
title_short | PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats |
title_sort | pten and akt/gsk-3β/crmp-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after sah in rats |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720672/ https://www.ncbi.nlm.nih.gov/pubmed/35005122 http://dx.doi.org/10.1016/j.gendis.2020.05.002 |
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