Journal
NEUROCHEMICAL RESEARCH
Volume 44, Issue 4, Pages 811-828Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-018-02714-z
Keywords
Traumatic brain injury; Exosome; MiR-124; Microglia; Neurogenesis; TLR4
Categories
Funding
- National Natural Science Foundation of China [81471264]
- Science and Technology Development Fund of Airforce Military Medical University (Fourth Military Medical University) [2016XC178, 2016XC210]
Ask authors/readers for more resources
MicroRNA-124 (miR-124) is a brain specific miRNA that is highly expressed in microglia. The upregulation of miR-124 contributes to M2 polarization of microglia, which is beneficial to neurogenesis. Exosomes are lipid membrane vesicles that can deliver miR-124 into the brain. However, whether miR-124 enriched exosomes (Exo-miR-124) can regulate the polarization of microglia and affect hippocampus neurogenesis after traumatic brain injury (TBI) is unknown. To clarify this, the Exo-miR-124 was first constructed, and then was intravenously administrated into rats via tail vein with the dose of 3x10(9) particles/each rat at 24h post TBI. The polarization of microglia in hippocampus was evaluated through measuring the signature genes and cytokines of M1/M2 phenotype by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immune sorbent assay (ELISA) at 7/14/21/28 days after TBI. Hippocampus neurogenesis was evaluated through detecting the proliferation marker BrdU/SOX2 and differentiation marker BrdU/NeuN by immunofluorescence (IF) at 7 and 28days after TBI respectively. Neurological function was evaluated by neurological severity score (NSS) and morris water maze (MWM) at 7/14/21/28 and 24-28days after TBI respectively. To explore the underlying mechanisms, the mRNA expression of TLR4 pathway molecules in hippocampus were measured by RT-PCR, and the polarization of microglia and the activation of TLR4 pathway in BV2 cells were measured after exosome treatment as well. Results demonstrated that Exo-miR-124 treatment promoted the M2 polarization of microglia, enhanced neurogenesis in hippocampus, and improved function recovery after TBI. The M2 polarization effect of Exo-miR-124 was produced through inhibiting TLR4 pathway, which was verified in hippocampus and BV2 microglia. In conclusion, Exo-miR-124 treatment promoted M2 polarization of microglia and improved hippocampal neurogenesis and functional recovery after brain injury, which might be a strategy to improve the outcome of TBI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available