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Increased Microglial Exosomal miR-124-3p Alleviates Neurodegeneration and Improves Cognitive Outcome after rmTBI
Open accessAbstract
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 β-amyloid abnormalities and impaired cognitive function. Microglial exosomes have been reported to be involved in the transportation, distribution, and clearance of β-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 β-amyloid proteolytic breakdown, thereby inhibiting β-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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“When administered intravenously, these exosomes were found to inhibit neuronal inflammation and autophagy, enhance neurogenesis, and consequently improve neurological outcomes in mice [169].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [169]
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“Ge et al. discovered that miR-124 is abundantly present in sEVs derived from M2-microglia.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [169]
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“Notably, miR-124-3p within these exosomes was transferred to hippocampal neurons, where it mitigated neurodegeneration by targeting the Rela/ApoE signaling pathway.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [169]
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“Specifically, in mice models of repetitive mild TBI, these microglial exosomes were observed to be internalized by neurons in the injured brain.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [169]
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Metadata
- Authors
- Ge, X., Guo, M., Hu, T., Li, W., Huang, S., Yin, Z., Li, Y., Chen, F., Zhu, L., Kang, C., Jiang, R., Lei, P., & Zhang, J.
- Affiliations
- Tianjin Medical University General Hospital (CN)
- Corresponding author
- Jiang, Rongcai
- Lei, Ping
- Zhang, Jianning
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 28
- Issue
- 2
- Pages
- 503-522
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC7001001
- OpenAlex
- W2990551073
- Cited by
- 242
- References
- 67
- Citations by year
- 2026: 26 · 2025: 50 · 2024: 40 · 2023: 42 · 2022: 37 · 2021: 34 · 2020: 13
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81501055, 81772060, 81720108015, 81671221)
- Tianjin Municipal Science and Technology Commission Natural Fund Project (18JCQNJC81100)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- repetitive mild traumatic brain injury, miR-124-3p, neurodegeneration, cognitive impairment, amyloid-beta, Alzheimer's disease, exosome therapy, hippocampal neurons, microglia
- MeSH terms
- Animals, Apolipoproteins E, Brain Concussion, Cognition, Disease Models, Animal, Male, Models, Biological, Neurons, Severity of Illness Index, Signal Transduction, Microglia, Computational Biology, Neurodegenerative Diseases, Gene Expression Profiling, RNA Interference, MicroRNAs, Mice, Transcription Factor RelA, Exosomes
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