Frontiers in Genetics (Mar 2021)
MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke
- Fangfang Zhao,
- Fangfang Zhao,
- Haiping Zhao,
- Haiping Zhao,
- Junfen Fan,
- Junfen Fan,
- Rongliang Wang,
- Rongliang Wang,
- Ziping Han,
- Ziping Han,
- Zhen Tao,
- Zhen Tao,
- Yangmin Zheng,
- Yangmin Zheng,
- Feng Yan,
- Feng Yan,
- Yuyou Huang,
- Yuyou Huang,
- Lei Yu,
- Lei Yu,
- Xu Zhang,
- Xu Zhang,
- Xiaolong Qi,
- Xiaolong Qi,
- Lianfeng Zhang,
- Lianfeng Zhang,
- Yumin Luo,
- Yumin Luo,
- Yuanwu Ma,
- Yuanwu Ma
Affiliations
- Fangfang Zhao
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Fangfang Zhao
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Haiping Zhao
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Haiping Zhao
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Junfen Fan
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Junfen Fan
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Rongliang Wang
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Rongliang Wang
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Ziping Han
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Ziping Han
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Zhen Tao
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Zhen Tao
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Yangmin Zheng
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Yangmin Zheng
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Feng Yan
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Feng Yan
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Yuyou Huang
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Yuyou Huang
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Lei Yu
- Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC) and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China
- Lei Yu
- Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
- Xu Zhang
- Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC) and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China
- Xu Zhang
- Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
- Xiaolong Qi
- Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC) and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China
- Xiaolong Qi
- Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
- Lianfeng Zhang
- Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC) and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China
- Lianfeng Zhang
- Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
- Yumin Luo
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
- Yumin Luo
- Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
- Yuanwu Ma
- Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC) and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China
- Yuanwu Ma
- Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
- DOI
- https://doi.org/10.3389/fgene.2021.642079
- Journal volume & issue
-
Vol. 12
Abstract
ObjectiveBy exploring the effects of miR-29a-5p knockout on neurological damage after acute ischemic stroke, we aim to deepen understanding of the molecular mechanisms of post-ischemic injury and thus provide new ideas for the treatment of ischemic brain injury.MethodsmiR-29a-5p knockout rats and wild-type SD rats were subjected to transient middle cerebral artery occlusion (MCAO). miR-29a levels in plasma, cortex, and basal ganglia of ischemic rats, and in plasma and neutrophils of ischemic stroke patients, as well as hypoxic glial cells were detected by real-time PCR. The infarct volume was detected by TTC staining and the activation of astrocytes and microglia was detected by western blotting.ResultsThe expression of miR-29a-5p was decreased in parallel in blood and brain tissue of rat MCAO models. Besides, miR-29a-5p levels were reduced in the peripheral blood of acute stroke patients. Knockout of miR-29a enhanced infarct volume of the MCAO rat model, and miR-29a knockout showed M1 polarization of microglia in the MCAO rat brain. miR-29a knockout in rats after MCAO promoted astrocyte proliferation and increased glutamate release.ConclusionKnockout of miR-29a in rats promoted M1 microglial polarization and increased glutamate release, thereby aggravating neurological damage in experimental stroke rat models.
Keywords
