Open AccessIdentification of microRNAs with Dysregulated Expression in Status Epilepticus Induced Epileptogenesis
Author(s) -
Mykaella Andrade de Araújo,
Thalita Ewellyn Batista Sales Marques,
Shirley Octacílio-Silva,
Carmem Lúcia de Arroxelas-Silva,
Marcelo Pereira,
José Eduardo Peixoto-Santos,
Ludmyla Kandratavicius,
João Pereira Leite,
Norberto GarciaCairasco,
Olagide Wagner de Castro,
Marcelo Duzzioni,
Geraldo Aleixo Silva Passos,
Maria Luísa Paçó-Larson,
Daniel Leite Góes Gitaí
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0163855
Subject(s) - status epilepticus , epileptogenesis , epilepsy , microrna , pilocarpine , hippocampal formation , hippocampus , biology , gene expression profiling , microarray analysis techniques , gene expression , neuroscience , gene , genetics
The involvement of miRNA in mesial temporal lobe epilepsy (MTLE) pathogenesis has increasingly become a focus of epigenetic studies. Despite advances, the number of known miRNAs with a consistent expression response during epileptogenesis is still small. Addressing this situation requires additional miRNA profiling studies coupled to detailed individual expression analyses. Here, we perform a miRNA microarray analysis of the hippocampus of Wistar rats 24 hours after intra-hippocampal pilocarpine-induced Status Epilepticus (H-PILO SE). We identified 73 miRNAs that undergo significant changes, of which 36 were up-regulated and 37 were down-regulated. To validate, we selected 5 of these (10a-5p, 128a-3p, 196b-5p, 352 and 324-3p) for RT-qPCR analysis. Our results confirmed that miR-352 and 196b-5p levels were significantly higher and miR-128a-3p levels were significantly lower in the hippocampus of H-PILO SE rats. We also evaluated whether the 3 miRNAs show a dysregulated hippocampal expression at three time periods (0h, 24h and chronic phase) after systemic pilocarpine-induced status epilepticus (S-PILO SE). We demonstrate that miR-128a-3p transcripts are significantly reduced at all time points compared to the naïve group. Moreover, miR-196b-5p was significantly higher only at 24h post-SE, while miR-352 transcripts were significantly up-regulated after 24h and in chronic phase (epileptic) rats. Finally, when we compared hippocampi of epileptic and non-epileptic humans, we observed that transcript levels of miRNAs show similar trends to the animal models. In summary, we successfully identified two novel dysregulated miRNAs (196b-5p and 352) and confirmed miR-128a-3p downregulation in SE-induced epileptogenesis. Further functional assays are required to understand the role of these miRNAs in MTLE pathogenesis.