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Microglia exosomal miRNA-137 attenuates ischemic brain injury through targeting Notch1
- Source :
- Aging (Albany NY)
- Publication Year :
- 2021
- Publisher :
- Impact Journals, LLC, 2021.
-
Abstract
- Microglia are the resident immune cells in the central nervous system and play an essential role in brain homeostasis and neuroprotection in brain diseases. Exosomes are crucial in intercellular communication by transporting bioactive miRNAs. Thus, this study aimed to investigate the function of microglial exosome in the presence of ischemic injury and related mechanism. Oxygen-glucose deprivation (OGD)-treated neurons and transient middle cerebral artery occlusion (TMCAO)-treated mice were applied in this study. Western blotting, RT-PCR, RNA-seq, luciferase reporter assay, transmission electron microscope, nanoparticle tracking analysis, immunohistochemistry, TUNEL and LDH assays, and behavioral assay were applied in mechanistic and functional studies. The results demonstrated that exosomes derived from microglia in M2 phenotype (BV2-Exo) were internalized by neurons and attenuated neuronal apoptosis in response to ischemic injury in vitro and in vivo. BV2-Exo also decreased infarct volume and behavioral deficits in ischemic mice. Exosomal miRNA-137 was upregulated in BV2-Exo and participated in the partial neuroprotective effect of BV2-Exo. Furthermore, Notch1 was a directly targeting gene of exosomal miRNA-137. In conclusion, these results suggest that BV2-Exo alleviates ischemia-reperfusion brain injury through transporting exosomal miRNA-137. This study provides novel insight into microglial exosomes-based therapies for the treatment of ischemic brain injury.
- Subjects :
- Aging
Central nervous system
microglia
Apoptosis
Exosomes
Exosome
Neuroprotection
Brain Ischemia
Mice
Downregulation and upregulation
In vivo
medicine
exosome
Animals
Receptor, Notch1
Neurons
Notch1
TUNEL assay
Microglia
business.industry
Infarction, Middle Cerebral Artery
Cell Biology
Microvesicles
Cell biology
Disease Models, Animal
MicroRNAs
medicine.anatomical_structure
Reperfusion Injury
miRNA-137
business
ischemic injury
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....c7ee27fbc7d48f0c06616169d7714a3d