Identification of microRNAs with Dysregulated Expression in Status Epilepticus Induced Epileptogenesis.

Autor: Araújo MA; Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil., Marques TE; Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil., Octacílio-Silva S; Department of Morphology, Health and Biological Sciences Center, Federal University of Sergipe, Aracajú, Sergipe, Brazil., Arroxelas-Silva CL; Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil., Pereira MG; Department of Biochemistry, Institute of Biological Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., Peixoto-Santos JE; Division of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Kandratavicius L; Division of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Leite JP; Division of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Garcia-Cairasco N; Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Castro OW; Department of Physiology and Pharmacology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil., Duzzioni M; Department of Physiology and Pharmacology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil., Passos GA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Paçó-Larson ML; Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Góes Gitaí DL; Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Oct 03; Vol. 11 (10), pp. e0163855. Date of Electronic Publication: 2016 Oct 03 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0163855
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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