MiR-106b-5p upregulation is associated with microglial activation and inflammation in the mouse hippocampus following status epilepticus.

Abstract

To investigate the association of miR-106b-5p with neuroinflammation and microglial activation in a status epilepticus (SE) mouse model. We examined changes in the expression of microRNA-106b-5p (miRNA-106b-5p), repulsive guidance molecule A (RGMa), triggering receptor expressed on myeloid cells 2 (TREM2), and the microglia-related markers interleukin (IL)-1β, IL-4, IL-6, IL-10, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1) in the mouse hippocampus of the lithium-pilocarpine-induced SE mouse model. Eighty-four female C57BL/6 mice were randomly divided into a normal control group (n = 12), and six SE groups (n = 12/group), which were monitored at 6h and at 1, 3, 7, 14, and 21days (d) post-SE induction. Unlike in the dentate gyrus, immunohistochemical staining revealed prominent neuronal swelling at 6h, significant neuronal loss and apoptosis on day 3, and recovery by day 14 in the hippocampal cornu ammonis (CA)1 and CA3 pyramidal cells in SE mice. We noted elevated levels of miRNA-106b-5p and all microglia-related markers, which peaked at 3days post-SE, except IL-4, which peaked at 7days post-SE, indicating inflammation and microglial activation. RGMa and TREM2 levels decreased at 6h post-SE. All markers but miRNA-106b-5p, RGMa, and TREM2 returned to baseline levels at 21days post-SE. Dual luciferase reporter gene assay showed that microRNA-106b-5p can interact with RGMa. We observed that miR-106b-5p level increased while both RGMa and TREM2 levels decreased post-SE and showed associations with microglial activation and inflammation in the mouse hippocampus, suggesting their potential as SE therapeutic targets.