Modulation of miR-146a/complement factor H-mediated inflammatory responses in a rat model of temporal lobe epilepsy

Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). miRNAs represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune system homoeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE. Prominent up-regulation of miR-146a activation was evident in 1 week after status epilepticus (SE) and persisted in the chronic phase. The predicted miR-146a's target complement factor H (CFH) mRNA and protein expression was also down-regulated in TLE rat model. Furthermore, transfection of miR-146a mimics in neuronal and glial cells down-regulated CFH mRNA and protein levels respectively. Luciferase reporter assays demonstrated that miR-146a down-regulated CFH mRNA expression via 3'-UTR pairing. Down-regulating miR-146a by intracerebroventricular injection of antagomir-146a enhanced the hippocampal expression of CFH in TLE model and decreased seizure susceptibility. These findings suggest that immunopathological deficits associated with TLE can in part be explained by a generalized miR-146a-mediated down-regulation of CFH that may contribute to epileptogenesis in a rat model of TLE.