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...
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300672 |
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| author | Hong Chen Chao Zhou Jianfeng Zheng Zhaosi Zhang Yongbing Deng Chongjie Cheng Zongduo Guo Gang Huo Cheng Yin Xiaochuan Sun |
| author_facet | Hong Chen Chao Zhou Jianfeng Zheng Zhaosi Zhang Yongbing Deng Chongjie Cheng Zongduo Guo Gang Huo Cheng Yin Xiaochuan Sun |
| author_sort | Hong Chen |
| collection | DOAJ |
| 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. |
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| language | English |
| last_indexed | 2024-03-12T09:08:12Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-b36b18aa5f544549886a9528ce3e52ca2023-09-02T15:13:18ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422022-01-0191252267PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in ratsHong Chen0Chao Zhou1Jianfeng Zheng2Zhaosi Zhang3Yongbing Deng4Chongjie Cheng5Zongduo Guo6Gang Huo7Cheng Yin8Xiaochuan Sun9Department of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery of the Chongqing Emergency Medical Center, Chongqing 400014, PR ChinaDepartment of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, PR China; Corresponding author. Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, PR China.Department of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; Corresponding author. Department of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.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.http://www.sciencedirect.com/science/article/pii/S2352304220300672AKT/GSK-3β/CRMP-2 pathwayAxonal injuryEarly brain injuryNeuronal apoptosisPTENSubarachnoid hemorrhage |
| spellingShingle | Hong Chen Chao Zhou Jianfeng Zheng Zhaosi Zhang Yongbing Deng Chongjie Cheng Zongduo Guo Gang Huo Cheng Yin Xiaochuan Sun 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 Genes and Diseases AKT/GSK-3β/CRMP-2 pathway Axonal injury Early brain injury Neuronal apoptosis PTEN Subarachnoid hemorrhage |
| 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 | AKT/GSK-3β/CRMP-2 pathway Axonal injury Early brain injury Neuronal apoptosis PTEN Subarachnoid hemorrhage |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300672 |
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