MicroRNA-124 attenuates PTSD-like behaviors and reduces the level of inflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats following single-prolonged stress

Exp Neurol. 2022 Oct:356:114154. doi: 10.1016/j.expneurol.2022.114154. Epub 2022 Jun 24.

Abstract

Background: MicroRNA-124-3p (miR-124) plays an important role in neuroprotective functions in various neurological disorders, but whether miR-124 participates in the pathological progression of posttraumatic stress disorder (PTSD) remains poorly understood.

Methods: In the present study, we assessed the level of neuroinflammation in the hippocampus of rats exposed to single-prolonged stress (SPS) by Western blot and immunofluorescence staining, while the effect of miR-124 on PTSD-like behaviors was evaluated by behavioral test.

Results: Our results showed that the level of miR-124 in the hippocampus of rats exposed to SPS was downregulated and that the upregulation of miR-124 could alleviate the PTSD-like behaviors of SPS rats. This effect of miR-124 might be achieved through TNF receptor-associated Factor 6 (TRAF6), which is a target gene of miR-124 and plays an important role in the immune and inflammatory reaction by regulating nuclear factor kappa-B (NF-κB). Furthermore, we found that miR-124 not only decreased the level of proinflammatory cytokines but also increased the expression levels of synaptic proteins (PSD95 and synapsin I) and regulated the morphology of neurons.

Conclusion: These results suggested that miR-124 might attenuate PTSD-like behaviors and decrease the level of proinflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats exposed to SPS.

Keywords: Hippocampus; Neuroinflammation; PTSD; TRAF6; microRNA-124.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Hippocampus / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B / genetics
  • Rats
  • Stress Disorders, Post-Traumatic* / metabolism
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • Cytokines
  • MIRN124 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • TNF Receptor-Associated Factor 6