Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models.

• Type of Material: Article
• Authors: Raymond Dingledine, Emory University; Douglas A. Coulter, Children's Hospital of Philadelphia; Brita Fritsch, University Hospital Freiburg; Jan A. Gorter, University of Amsterdam; Nadia Lelutiu, Emory University; James McNamara, Duke University; J. Victor Nadler, Duke University; Asla Pitkänen, University of Eastern Finland; Michael A. Rogawski, University of California Davis; Pate Skene, Duke University; Robert S. Sloviter, Morehouse School of Medicine; Yu Wang, Duke University; Wytse J. Wadman, University of Amsterdam; Claude Wasterlain, University of California Los Angeles; Avtar Roopra, University of Wisconsin
• Language: English
• Date: 2017-05-09
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2017, The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/sdata.2017.61
• Title of Journal or Parent Work: Scientific Data
• ISSN: 2052-4463
• Volume: 4
• Start Page: 170061
• End Page: 170061
• Grant/Funding Information: This work was supported by NIH grants U01 NS058158 and R01NS097776 (RD), R21 NS03364 (AR & RD), R21 NS095187 (AR), CURE Challenge Award (AR), R01 NS056217 (JM), R01NS‐38108 (JVN), Nationaal Epilepsie Fonds (07-19), R01 NS038572 and R01082046 (DC), the Academy of Finland grants 272249 and 273909 (AP), RO1 NS13515, UO1 NS074926 and VHA Research Service (CW).
• Keywords: Epilepsy; Transcriptomics
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling. In each epilepsy model, RNA was harvested from laser-captured dentate granule cells from six rats at four time points early in the process of developing epilepsy, and data were collected from two independent laboratories in each rodent model except SSSE. Hierarchical clustering of differentially-expressed transcripts in the three SE models revealed complete separation between controls and SE rats isolated 1 day after SE. However, concordance of gene expression changes in the SE models was only 26-38% between laboratories, and 4.5% among models, validating the consortium approach. Transcripts with unusually highly variable control expression across laboratories provide a 'red herring' list for low-powered studies.