Talk abstracts

Talk on Wednesday 03:45-04:00pm submitted by Katelin Hansen

Genome-wide Analysis of Pathogenic Changes in mRNA Expression in a Mouse Model of Temporal Lobe Epilepsy

Katelin F. Hansen (Department of Neuroscience, Ohio State University), Kensuke Sakamoto (Department of Neuroscience, Ohio State University), Carl Pelz (Vollum Institute, Oregon Health & Sciences University), Soren Impey (Vollum Institute, Oregon Health & Sciences University), Karl Obrietan (Department of Neuroscience, Ohio State University)

Abstract:
Status epilepticus (SE) is life-threatening condition that often gives rise to the development of temporal lobe epilepsy (TLE). In rodent models, pilocarpine-evoked TLE follows a highly-stereotyped pattern of pathogenesis. However the molecular signaling events that couple SE to epileptogenesis are not well understood.
The advent of next-generation deep sequencing can provide needed insight into the mechanisms of epileptogenesis. Here, we take advantage of a high-throughput strategy to examine mRNA expression across pathological development of TLE. We performed whole transcriptome profiling to identify differentially expressed mRNAs at each phase of epileptogenesis (acute, seizure-silent, and chronic) and characterize distinct alterations in gene expression, as well as differential functional changes, at each timepoint.
Our results reveal that the hippocampal transcriptome is differentially regulated across the phases of epileptogenesis. While some genes were expressed over the entire course of progression, the each phase of pilocarpine-induced SE was largely unique in its transcriptional profile. Functional analysis revealed dynamic enrichment within the MAPK signaling pathway as function of time. Additionally, the nonbiased nature of high-throughput sequencing allowed for the identification of several novel noncoding transcripts that were induced over the course of epileptogenesis.
Transcriptional induction at each phase of epileptogenesis points to key molecular signaling mechanisms by which epileptic seizure is propagated. These findings offer new insight into the network of neuronal cellular signaling events that underlie SE and reveal novel molecular targets for treatment of TLE.

Keywords: Epilepsy, RNA-seq, Transcriptome