Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). MicroRNAs (miRNA) represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune-system homeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE. Prominent upregulation of miR-146a activation was evident at 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 downregulated in TLE rat model. Furthermore, transfection of miR-146a mimics in neuronal and glial cells downregulated CFH mRNA and protein levels, respectively. Luciferase reporter assays demonstrated that miR-146a downregulated CFH mRNA expression via 3'-untranslated-region (UTR) pairing. Downregulating miR-146a by intracerebroventricularly 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.
- Temporal lobe epilepsy
- Complement factor H
- ©2016 The Author(s)
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