Exogenous microRNA 322-5p Reduced Neuronal Inflammation via the TRAF6/IRF5/NF-kB Axis and Restored GAD1/GABA Expression in a Pilocarpine-induced Epileptic Rat Model

Objective: MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression at the posttranscriptional level. Some dysregulated miRNAs have been shown to play essential roles in epileptic development. This study aimed to determine if microRNA-322-5p regulates seizure and seizure damage by targeting the NFκB-TLR4 associated inflammatory signaling pathway.Methods: Pilocarpine-induced epileptic rat model was established. Immunohistochemical staining demonstrated the pathology of epilepsy. The expression of microRNA-322-5p, inflammatory markers, NF-kB, TLR4, IL-1β and IL-6, and synaptic inhibitory molecules, GAD1 and GABA, were assessed by a quantitative polymerase chain reaction, and western blotting, respectively.Results: The expression of microRNA-322-5p was significantly decreased in the SE (status epilepticus) rats compared with the normal counterparts. The reduction of miR-322-5p was accompanied by an increased level of pro‑inflammatory cytokines such as IL-6 and TNF-α via increased NF-kB expression and reduced GAD1 and GABA expression. The exogenously increased miR-322-5p level by mimic molecules significantly reduced the inflammatory profiles and increased GAD1 and GABA expressions in the S.E. rat brain compared to nontreated counterparts. Conclusions: Our findings suggest that the restoration of miR-322-5p resulted in a significantly reduced TRL4/IRF1/NF-kb associated inflammatory circuit and increased GAD1 and GABA expression. These findings suggest that miR-322-5p induction may be of therapeutic potential for neural damage as a result of repeated epileptic episodes.