The Phenotype Changes of Astrocyte During Different Ischemia Conditions
Objectives: Dementia is becoming a major health problem in the world, and chronic brain ischemia is an established important risk factor in predisposing this disease. Astrocytes, as one major part of the blood–brain barrier (BBB), are activated during chronic cerebral blood flow hypoperfusion. React...
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2024-12-01
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| author | Fei Meng Jing Cui Peng Wang Junhui Wang Jing Sun Liang Li |
| author_facet | Fei Meng Jing Cui Peng Wang Junhui Wang Jing Sun Liang Li |
| author_sort | Fei Meng |
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| description | Objectives: Dementia is becoming a major health problem in the world, and chronic brain ischemia is an established important risk factor in predisposing this disease. Astrocytes, as one major part of the blood–brain barrier (BBB), are activated during chronic cerebral blood flow hypoperfusion. Reactive astrocytes have been classified into phenotype pro-inflammatory type A1 or neuroprotective type A2. However, the specific subtype change of astrocyte and the mechanisms of chronic brain ischemia are still unknown. Methods: In order to depict the phenotype changes and their possible roles during this process, a rat bilateral common carotid artery occlusion model (BCAO) was employed in the present study. Meanwhile, the signaling pathways that possibly regulate these changes were investigated as well. Results: After four-week occlusion, astrocytes in the cortex of BCAO rats were shown to be the A2 phenotype, identified by the significant up-regulation of S100a10 accompanied by the down-regulation of Connexin 43 (CX43) protein. Next, we established in vitro hypoxia models, which were set up by stimulating primary astrocyte cultures from rat cortex with cobalt chloride, low glucose, or/and fibrinogen. Consistent with in vivo data, the cultured astrocytes also transformed into the A2 phenotype with the up-regulation of S100a10 and the down-regulation of CX43. In order to explore the mechanism of CX43 protein changes, C6 astrocyte cells were handled in both hypoxia and low-glucose stimulus, in which decreased pERK and pJNK expression were found. Conclusions: In conclusion, our data suggest that in chronic cerebral ischemia conditions, the gradual ischemic insults could promote the transformation of astrocytes into A2 type instead of A1 type, and the phosphorylation of CX43 was negatively regulated by the phosphorylation of ERK and JNK. Also, our data could provide some new evidence of how to leverage the endogenous astrocytes phenotype changes during CNS injury by promoting them to be “protector” and not “culprit”. |
| format | Article |
| id | doaj-art-2eabdff08c0b44edb46e7f4d8059da90 |
| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Brain Sciences |
| spelling | doaj-art-2eabdff08c0b44edb46e7f4d8059da902024-12-27T14:14:55ZengMDPI AGBrain Sciences2076-34252024-12-011412125610.3390/brainsci14121256The Phenotype Changes of Astrocyte During Different Ischemia ConditionsFei Meng0Jing Cui1Peng Wang2Junhui Wang3Jing Sun4Liang Li5Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 101100, ChinaDepartment of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital, Shandong University, Jinan 250012, ChinaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, CanadaDepartment of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaDepartment of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaObjectives: Dementia is becoming a major health problem in the world, and chronic brain ischemia is an established important risk factor in predisposing this disease. Astrocytes, as one major part of the blood–brain barrier (BBB), are activated during chronic cerebral blood flow hypoperfusion. Reactive astrocytes have been classified into phenotype pro-inflammatory type A1 or neuroprotective type A2. However, the specific subtype change of astrocyte and the mechanisms of chronic brain ischemia are still unknown. Methods: In order to depict the phenotype changes and their possible roles during this process, a rat bilateral common carotid artery occlusion model (BCAO) was employed in the present study. Meanwhile, the signaling pathways that possibly regulate these changes were investigated as well. Results: After four-week occlusion, astrocytes in the cortex of BCAO rats were shown to be the A2 phenotype, identified by the significant up-regulation of S100a10 accompanied by the down-regulation of Connexin 43 (CX43) protein. Next, we established in vitro hypoxia models, which were set up by stimulating primary astrocyte cultures from rat cortex with cobalt chloride, low glucose, or/and fibrinogen. Consistent with in vivo data, the cultured astrocytes also transformed into the A2 phenotype with the up-regulation of S100a10 and the down-regulation of CX43. In order to explore the mechanism of CX43 protein changes, C6 astrocyte cells were handled in both hypoxia and low-glucose stimulus, in which decreased pERK and pJNK expression were found. Conclusions: In conclusion, our data suggest that in chronic cerebral ischemia conditions, the gradual ischemic insults could promote the transformation of astrocytes into A2 type instead of A1 type, and the phosphorylation of CX43 was negatively regulated by the phosphorylation of ERK and JNK. Also, our data could provide some new evidence of how to leverage the endogenous astrocytes phenotype changes during CNS injury by promoting them to be “protector” and not “culprit”.https://www.mdpi.com/2076-3425/14/12/1256dementiaischemiaastrocytesA2 phenotypeConnexin 43 |
| spellingShingle | Fei Meng Jing Cui Peng Wang Junhui Wang Jing Sun Liang Li The Phenotype Changes of Astrocyte During Different Ischemia Conditions Brain Sciences dementia ischemia astrocytes A2 phenotype Connexin 43 |
| title | The Phenotype Changes of Astrocyte During Different Ischemia Conditions |
| title_full | The Phenotype Changes of Astrocyte During Different Ischemia Conditions |
| title_fullStr | The Phenotype Changes of Astrocyte During Different Ischemia Conditions |
| title_full_unstemmed | The Phenotype Changes of Astrocyte During Different Ischemia Conditions |
| title_short | The Phenotype Changes of Astrocyte During Different Ischemia Conditions |
| title_sort | phenotype changes of astrocyte during different ischemia conditions |
| topic | dementia ischemia astrocytes A2 phenotype Connexin 43 |
| url | https://www.mdpi.com/2076-3425/14/12/1256 |
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