Manipulação funcional de microRNAs na epilepsia do lobo temporal induzida por Status Epilepticus

Abstract

Numerous evidences have shown that the SE-induced epileptogenesis is accompanied by a miRNAome remapping, encouraging a burst of functional studies to understand the role and the clinical potential of these molecules on the acquisition and maintenance of an epilepticprone state. Here, we performed a systematic review to assess the functional interference studies of miRNAs on SE-induced epileptogenesis. We screened 4732 unique citations from several library databases or EpimiRBase up to July 2020. The outcome measures included information on seizure activity, neurobiological process, cognitive and mood functions. Sixty-one studies met eligibility criteria, providing data regarding 36 miRs, of which 15 were investigated independently in at least two studies. The functional modulation elicited: i. anticonvulsant action on SE (20 miRs) or spontaneous recurrent seizure (17 miRs); ii. neuroprotective effects (25 miRs); iii. anti-inflammatory response (7 miRs); iv. cell gliosis decrease (5 miRs); v. a reduction in axonal and dendritic alterations (3 miRs) and vi. learning and memory improvement (6 miRs). The sole study that used an antagomir multiplex approach targeting miR-10a-5p, miR-21a-5p, and miR-142a-5p showed reduced severity of SE as well, reduced severity and occurrence of SRS. We discussed the anti-epileptic and disease-modification potential of these findings considering the data consistency on independent studies, the complementary effects of bi-direction modulation and the experimental design. Thus, the critical observation of these data, revealed gaps in knowledge about the effects of miRNA modulation on SE-induced epileptogenesis in experimental models of Temporal Lobe Epilepsy (TLE). The synthesis of this information, therefore, allows a panoramic view of the stage of investigation of these miRNAs and necessary steps are possible for the new studies to address before clinical application as therapeutic targets.