Modulation of Microglia M2 Polarization and Alleviation of Hippocampal Neuron Injury By MiR-106b-5p/RGMa in a Mouse Model of Status Epilepticus

Inflammation. 2022 Dec;45(6):2223-2242. doi: 10.1007/s10753-022-01686-1. Epub 2022 Jul 4.

Abstract

MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level. The miRNA miR-106b-5p has been linked to epilepsy, but its specific role and mechanism of action remain unclear. This was investigated in the present study using a mouse model of pilocarpine-induced status epilepticus and an in vitro system of HT22 hippocampal cells treated with Mg2+-free solution and cocultured with BV2 microglia cells. We found that inhibiting miR-106b-5p expression promoted microglia M2 polarization, reduced the inflammatory response, and alleviated neuronal injury. These effects involved modulation of the repulsive guidance molecule A (RGMa)-Rac1-c-Jun N-terminal kinase (JNK)/p38-mitogen-activated protein kinase (MAPK) signaling axis. Our results suggest that therapeutic strategies targeting miR-106b-5p or downstream factors can be effective in preventing epileptogenesis or treating epilepsy.

Keywords: epilepsy; inflammation.; miR-106b-5p; microRNA; microglia.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Hippocampus / metabolism
  • MicroRNAs* / metabolism
  • Microglia / metabolism
  • Neurons / metabolism
  • Status Epilepticus* / chemically induced
  • Status Epilepticus* / drug therapy
  • Status Epilepticus* / metabolism

Substances

  • MicroRNAs