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Increased Microglial Exosomal miR-124-3p Alleviates Neurodegeneration and Improves Cognitive Outcome after rmTBI.
Ge, Xintong; Guo, Mengtian; Hu, Tianpeng; Li, Wenzhu; Huang, Shan; Yin, Zhenyu; Li, Ying; Chen, Fanglian; Zhu, Luoyun; Kang, Chunsheng; Jiang, Rongcai; Lei, Ping; Zhang, Jianning.
Affiliation
  • Ge X; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Ner
  • Guo M; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Hu T; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Li W; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Huang S; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Yin Z; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Li Y; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Tianjin Neurological Institute, Tianjin 300052, China.
  • Chen F; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Tianjin Neurological Institute, Tianjin 300052, China.
  • Zhu L; Department of Medical Examination, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Kang C; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Tianjin Neurological Institute, Tianjin 300052, China.
  • Jiang R; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Ner
  • Lei P; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: leiping1974@163.com.
  • Zhang J; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Ner
Mol Ther ; 28(2): 503-522, 2020 02 05.
Article in En | MEDLINE | ID: mdl-31843449
ABSTRACT
Repetitive mild traumatic brain injury (rmTBI) is considered to be an important risk factor for long-term neurodegenerative disorders such as Alzheimer's disease, which is characterized by ß-amyloid abnormalities and impaired cognitive function. Microglial exosomes have been reported to be involved in the transportation, distribution, and clearance of ß-amyloid in Alzheimer's disease. However, their impacts on the development of neurodegeneration after rmTBI are not yet known. The role of miRNAs in microglial exosomes on regulating post-traumatic neurodegeneration was investigated in the present study. We demonstrated that miR-124-3p level in microglial exosomes from injured brain was significantly altered in the acute, sub-acute, and chronic phases after rmTBI. In in vitro experiments, microglial exosomes with upregulated miR-124-3p (EXO-124) alleviated neurodegeneration in repetitive scratch-injured neurons. The effects were exerted by miR-124-3p targeting Rela, an inhibitory transcription factor of ApoE that promotes the ß-amyloid proteolytic breakdown, thereby inhibiting ß-amyloid abnormalities. In mice with rmTBI, the intravenously injected microglial exosomes were taken up by neurons in injured brain. Besides, miR-124-3p in the exosomes was transferred into hippocampal neurons and alleviated neurodegeneration by targeting the Rela/ApoE signaling pathway. Consequently, EXO-124 treatments improved the cognitive outcome after rmTBI, suggesting a promising therapeutic strategy for future clinical translation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Concussion / Cognition / Microglia / Neurodegenerative Diseases / MicroRNAs / Exosomes Type of study: Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2020 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Concussion / Cognition / Microglia / Neurodegenerative Diseases / MicroRNAs / Exosomes Type of study: Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2020 Type: Article