IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region
Cognitive impairment is a major complication of cerebral ischemia–reperfusion (CIR) injury and has an important impact on the quality of life of patients. However, the precise mechanisms underlying cognitive impairment after CIR injury remain elusive. In the current study, we investigated the role o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923024000236 |
| _version_ | 1797281214020714496 |
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| author | Yanan Li Qi Zhang Xupeng Wang Fang Xu Junfang Niu Juan Zhao Qiujun Wang |
| author_facet | Yanan Li Qi Zhang Xupeng Wang Fang Xu Junfang Niu Juan Zhao Qiujun Wang |
| author_sort | Yanan Li |
| collection | DOAJ |
| description | Cognitive impairment is a major complication of cerebral ischemia–reperfusion (CIR) injury and has an important impact on the quality of life of patients. However, the precise mechanisms underlying cognitive impairment after CIR injury remain elusive. In the current study, we investigated the role of interleukin 17 A (IL-17A) on CIR injury-induced cognitive impairment in wild-type and IL-17A knockout mice using RNA sequencing analysis, neurological assessments, Golgi–Cox staining, dendritic spine analysis, immunofluorescence assay, and western blot analysis. RNA sequencing identified 195 CIR-induced differentially expressed genes (83 upregulated and 112 downregulated), highlighting several enriched biological processes (negative regulation of phosphorylation, transcription regulator complex, and receptor ligand activity) and signaling pathways (mitogen-activated protein kinase [MAPK], tumor necrosis factor, and IL-17 signaling pathways). We also injected adeno-associated virus into the bilateral hippocampal CA1 regions of CIR mice to upregulate or downregulate cyclic AMP response element-binding protein. IL-17A knockout activated the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway and further improved synaptic plasticity, structure, and function in CIR mice. Together, our findings suggest that IL-17A deficiency alleviates CIR injury by activating the ERK/MAPK signaling pathway and enhancing hippocampal synaptic plasticity. |
| first_indexed | 2024-03-07T16:54:09Z |
| format | Article |
| id | doaj.art-c169476088cb41899c98ec12ca4c3bf9 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-07T16:54:09Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-c169476088cb41899c98ec12ca4c3bf92024-03-03T04:28:52ZengElsevierBrain Research Bulletin1873-27472024-03-01208110890IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 regionYanan Li0Qi Zhang1Xupeng Wang2Fang Xu3Junfang Niu4Juan Zhao5Qiujun Wang6Department of Anesthesiology, the Third Hospital of Hebei Medical University, Hebei 050051, ChinaDepartment of Anesthesiology, Children’s Hospital of Hebei Province Affiliated to Hebei Medical University, Hebei 050031, ChinaDepartment of Anesthesiology, the Third Hospital of Hebei Medical University, Hebei 050051, ChinaDepartment of Anesthesiology, the Third Hospital of Hebei Medical University, Hebei 050051, ChinaDepartment of Anesthesiology, the Third Hospital of Hebei Medical University, Hebei 050051, ChinaExperimental Teaching Center, Hebei Medical University, Hebei 050001, ChinaDepartment of Anesthesiology, the Third Hospital of Hebei Medical University, Hebei 050051, China; Correspondence to: Department of Anesthesiology, the Third Hospital of Hebei Medical University, No.139 Ziqiang Road, Shijiazhuang City, Hebei Province 050051, China.Cognitive impairment is a major complication of cerebral ischemia–reperfusion (CIR) injury and has an important impact on the quality of life of patients. However, the precise mechanisms underlying cognitive impairment after CIR injury remain elusive. In the current study, we investigated the role of interleukin 17 A (IL-17A) on CIR injury-induced cognitive impairment in wild-type and IL-17A knockout mice using RNA sequencing analysis, neurological assessments, Golgi–Cox staining, dendritic spine analysis, immunofluorescence assay, and western blot analysis. RNA sequencing identified 195 CIR-induced differentially expressed genes (83 upregulated and 112 downregulated), highlighting several enriched biological processes (negative regulation of phosphorylation, transcription regulator complex, and receptor ligand activity) and signaling pathways (mitogen-activated protein kinase [MAPK], tumor necrosis factor, and IL-17 signaling pathways). We also injected adeno-associated virus into the bilateral hippocampal CA1 regions of CIR mice to upregulate or downregulate cyclic AMP response element-binding protein. IL-17A knockout activated the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway and further improved synaptic plasticity, structure, and function in CIR mice. Together, our findings suggest that IL-17A deficiency alleviates CIR injury by activating the ERK/MAPK signaling pathway and enhancing hippocampal synaptic plasticity.http://www.sciencedirect.com/science/article/pii/S0361923024000236IL-17ACerebral ischemia-reperfusionSynaptic plasticityRNA sequencingERK/MAPK signaling pathway |
| spellingShingle | Yanan Li Qi Zhang Xupeng Wang Fang Xu Junfang Niu Juan Zhao Qiujun Wang IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region Brain Research Bulletin IL-17A Cerebral ischemia-reperfusion Synaptic plasticity RNA sequencing ERK/MAPK signaling pathway |
| title | IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region |
| title_full | IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region |
| title_fullStr | IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region |
| title_full_unstemmed | IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region |
| title_short | IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region |
| title_sort | il 17a deficiency alleviates cerebral ischemia reperfusion injury via activating erk mapk pathway in hippocampal ca1 region |
| topic | IL-17A Cerebral ischemia-reperfusion Synaptic plasticity RNA sequencing ERK/MAPK signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0361923024000236 |
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