Electroacupuncture treatment enhances synaptic plasticity in middle cerebral artery occlusion mice via the miR-670-3p/HMGB1 axis.

Abstract

Background: Electroacupuncture (EA) is a physical therapy of traditional Chinese medicine, which has been widely used in clinical practice. This paper was designed to explore the effect of EA treatment on synaptic plasticity in mice subjected to middle cerebral artery occlusion (MCAO) and to elucidate the associated molecular mechanisms.

Methods: After MCAO modeling, C57BL/6 mice underwent EA treatment or/and miR-670-3p mimic injection, followed by assessment of neurological deficit by modified neurological severity score (mNSS) and evaluation on cerebral infarction area by TTC staining. The changes of synaptic ultrastructure related parameters were observed using transmission electron microscopy (TEM). The expression levels of miR-670-3p, HMGB1, TLR4/NF-κB pathway related proteins, and synaptic associated proteins (synapsin 1, PSD95, BDNF, and GAP43) were quantified by RT-qPCR and western blot analysis. The binding relationship between miR-670-3p and HMGB1 was assessed through dual-luciferase reporter assays and RNA pull down assays.

Results: Mice underwent EA treatment or miR-670-3p mimic injection exhibited increased miR-670-3p expression, reduced expression levels of HMGB1 and TLR4/NF-κB pathway related proteins, improved neurological function, and enhanced synaptic plasticity. Furthermore, the combination of EA treatment and miR-670-3p mimic injection produced a synergistic effect, further amplifying these outcomes. Mechanistically, miR-670-3p was found to negatively regulate HMGB1.

Conclusion: EA treatment enhances synaptic plasticity in MCAO mice by promoting miR-670-3p expression to negatively regulate the HMGB1/TLR4/NF-κB pathway.