Skip to main content
Journal cover image

Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury.

Publication ,  Journal Article
Li, D; Huang, S; Yin, Z; Zhu, J; Ge, X; Han, Z; Tan, J; Zhang, S; Zhao, J; Chen, F; Wang, H; Lei, P
Published in: Neurochem Res
August 2019

In our recent study, we observed consistent increases in miR-124-3p levels in exosomes derived from cultured BV2 microglia which was treated with repetitive traumatic brain injury (rTBI) mouse model brain extracts. To clarify the mechanisms underlying increases in microglia-derived exosomal miR-124-3p and their role in regulating neuronal autophagy after TBI, we investigated the impact of exosomal miR-124-3p on neuronal autophagy in scratch-injured HT22 neurons and rTBI mice. We harvested injured brain extracts from rTBI mice at 3 to 21 days post injury (DPI) for the treatment of cultured BV2 microglia in vitro. We observed significant induction of autophagy following TBI in vitro, and that inhibition of activated neuronal autophagy could protect against trauma-induced injury. Our results indicated that co-culture of injured HT22 neurons with miR-124-3p overexpressing BV2 microglia exerted a protective effect by inhibiting neuronal autophagy in scratch-injured neurons. Further research revealed that these effects were achieved mainly via upregulation of exosomal miR-124-3p, and that Focal adhesion kinase family-interacting protein of 200 kDa (FIP200) plays a key role in trauma-induced autophagy. Injection of exosomes into the vena caudalis in in vivo experiments revealed that exosomal miR-124-3p was associated with decreases in the modified neurological severity score (mNSS) and improvements in Morris water maze (MWM) test results in rTBI mice. Altogether, our results indicate that increased miR-124-3p in microglial exosomes following TBI may inhibit neuronal autophagy and protect against nerve injury via their transfer into neurons. Thus, treatment with microglial exosomes enriched with miR-124-3p may represent a novel therapeutic strategy for the treatment of nerve injury after TBI.

Duke Scholars

Published In

Neurochem Res

DOI

EISSN

1573-6903

Publication Date

August 2019

Volume

44

Issue

8

Start / End Page

1903 / 1923

Location

United States

Related Subject Headings

  • Neurons
  • Neurology & Neurosurgery
  • Microglia
  • MicroRNAs
  • Mice, Inbred C57BL
  • Male
  • Exosomes
  • Cell Line
  • Brain Injuries, Traumatic
  • Autophagy-Related Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, D., Huang, S., Yin, Z., Zhu, J., Ge, X., Han, Z., … Lei, P. (2019). Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury. Neurochem Res, 44(8), 1903–1923. https://doi.org/10.1007/s11064-019-02825-1
Li, Dai, Shan Huang, Zhenyu Yin, Jialin Zhu, Xintong Ge, Zhaoli Han, Jin Tan, et al. “Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury.Neurochem Res 44, no. 8 (August 2019): 1903–23. https://doi.org/10.1007/s11064-019-02825-1.
Li, Dai, et al. “Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury.Neurochem Res, vol. 44, no. 8, Aug. 2019, pp. 1903–23. Pubmed, doi:10.1007/s11064-019-02825-1.
Li D, Huang S, Yin Z, Zhu J, Ge X, Han Z, Tan J, Zhang S, Zhao J, Chen F, Wang H, Lei P. Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury. Neurochem Res. 2019 Aug;44(8):1903–1923.
Journal cover image

Published In

Neurochem Res

DOI

EISSN

1573-6903

Publication Date

August 2019

Volume

44

Issue

8

Start / End Page

1903 / 1923

Location

United States

Related Subject Headings

  • Neurons
  • Neurology & Neurosurgery
  • Microglia
  • MicroRNAs
  • Mice, Inbred C57BL
  • Male
  • Exosomes
  • Cell Line
  • Brain Injuries, Traumatic
  • Autophagy-Related Proteins