PT  - JOURNAL ARTICLE
AU  - Prashant K. Srivastava
AU  - Paolo Roncon
AU  - Katarzyna Lukasiuk
AU  - Jan A. Gorter
AU  - Eleonora Aronica
AU  - Asla Pitkänen
AU  - Enrico Petretto
AU  - Michael R. Johnson
AU  - Michele Simonato
TI  - Meta-analysis of microRNAs dysregulated in the hippocampal dentate gyrus of animal models of epilepsy
AID  - 10.1523/ENEURO.0152-17.2017
DP  - 2017 Dec 13
TA  - eneuro
PG  - ENEURO.0152-17.2017
4099  - http://www.eneuro.org/content/early/2017/12/13/ENEURO.0152-17.2017.short
4100  - http://www.eneuro.org/content/early/2017/12/13/ENEURO.0152-17.2017.full
AB  - The identification of mechanisms transforming normal to seizure-generating tissue after brain injury is key to developing new antiepileptogenic treatments. MiRNAs may act as regulators and potential treatment targets for epileptogenesis. Here, we undertook a meta-analysis of changes in miRNA expression in the hippocampal dentate gyrus following an epileptogenic insult in three epilepsy models. We identified 26 miRNAs significantly differentially expressed during epileptogenesis, and 5 differentially expressed in chronic epilepsy. Of these, 13 were not identified in any of the individual studies. To assess the role of these miRNAs, we predicted their mRNA targets and then filtered the list to include only target genes expressed in dentate gyrus and negatively correlated with miRNA expression. Functional enrichment analysis of mRNA targets of miRNAs dysregulated during epileptogenesis suggested a role for molecular processes related to inflammation and synaptic function. Our results identify new miRNAs associated with epileptogenesis from existing data, highlighting the utility of meta-analysis in maximizing value from pre-clinical data.Significance Statement Meta-analyses of data from human research studies are an invaluable tool, and the methods to conduct these investigations are well established. However, meta-analysis of preclinical data are rarely undertaken, due to the typically small sample sizes and the substantial heterogeneity between studies. We implemented a meta-analysis of microRNA (miRNA) expression changes in animal studies of epilepsy. This is the first study of its kind in the field of epilepsy and one of the first in preclinical research. Our analyses identify new miRNAs associated with epileptogenesis and epilepsy, highlighting common mechanisms across different animal models. These miRNAs and their predicted effects on gene expression generate new hypotheses about the causes of epilepsy that will prompt new studies in the field.