Since aberrant miRNA expression has been implicated in numerous brain diseases, we studied miRNA expression and miRNA regulation
of important signaling pathways during temporal lobe epileptogenesis in order to identify possible targets for epilepsy therapy.
The temporal profile of miRNA expression was analyzed in three brain regions (CA1; dentate gyrus, DG; parahippocampal cortex,
PHC) associated with epileptogenesis in a rat model for temporal lobe epilepsy. Tissue was obtained after electrically-induced
status epilepticus (SE) at 1day (n=5), 1week (n=5) and 3-4months (n=5), and compared with control tissue (n=10) using the
Exiqon microRNA arrays which contain capture probes targeting all miRNAs for rat (p<0.01, and a 1.5 fold up- or downregulation).
Expression of three blood plasma miRNAs from the same group of rats was also investigated in rats in order to determine whether
plasma miRNAs could serve as potential biomarkers of the epileptogenic process. Molecular pathways potentially altered by
the expression of multiple miRNAs were identified using a web-based algorithm, DIANA. In CA1 and DG, more upregulated than
downregulated miRNAs were present during each stage after SE. The highest numbers of upregulated miRNAs were encountered during
the chronic stage in the DG. In PHC, a high number of downregulated miRNAs were detected. Key pathways involved, based upon
quantitatively altered miRNA expression were: axon guidance, MAPK signaling pathway, focal adhesion, TGFbeta, ErbB-, Wnt-
and mTOR signaling, and regulation of actin skeleton. Expression of plasma miRNAs was differentially regulated after induction
of SE. This study identified several signaling pathways possibly involved in temporal lobe epileptogenesis, not previously
indicated by RNA microarray studies. These include miRNAs that regulate the ErbB and Wnt pathways and focal adhesion, which
may represent interesting new targets for therapeutic interventions.