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Epilepsy Benchmark IA3

Research @ NINDS
Epilepsy
Highlights
Judith Hoyer Lecture on Epilepsy

Curing the Epilepsies 2013: Pathways Forward

Resource Links
Anticonvulsant Screening Program (ASP)

NIH RePORTER is an electronic tool that allows users to search a repository of NIH-funded research projects and access publications and patents resulting from NIH funding.

Epilepsy Clinical Trials

Resources for Scientists

MedlinePlus

Contacts
Brandy Fureman, Ph.D.
Program Director, Channels Synapses & Circuits Cluster
furemanb@mail.nih.gov

Deborah Hirtz, M.D.
Program Director, Division of Extramural Research
dh83f@nih.gov

John Kehne, Ph.D.
Program Director, Anticonvulsant Screening Program
john.kehne@nih.gov

Randall Stewart, Ph.D.
Program Director, Extramural Research Program
rs416y@nih.gov

Vicky Whittemore, Ph.D.
Program Director, Channels, Synapses & Neural Circuits Cluster
vicky.whittemore@nih.gov

 

Epilepsy Benchmark IA3

Benchmark Area I: Understanding basic mechanisms of epileptogenesis

Section A: Discover the range of anatomical, physiological, and molecular substrates associated with the epilepsies; define unambiguous markers of epileptogenicity.

Specific Benchmark 3: Establish a collaborative network that enables investigators to compare results of gene-chip analyses arising from different models of epileptogenesis and epilepsy.


2005 Report submitted by Benchmark Steward(s):
Raymond Dingledine, Ph.D. (Emory University School of Medicine)
Randall Stewart, Ph.D. (National Institute of Neurological Disorders and Stroke)

Background of the benchmark goal:
DNA microarrays allow researchers to examine changes in gene expression of nearly every gene in the genome simultaneously. Validated results from DNA microarray experiments are then used to generate new hypotheses about the process of epileptogenesis, for example.

Current status of field:

Activities update: 

One of the outcomes of the Workshop on Epilepsy Research and DNA Microarrays held in October 2002 was the formation of a consortium of researchers to study epileptogenesis in pilocarpine, kainate, self-sustaining status epilepticus (SSSE) and kindling rat models. The members of the consortium include Ray Dingledine, Jim McNamara, Victor Nadler, Claude Wasterlain, Bob Sloviter, Doug Coulter, Wytse Wadman and Asla Pitkanen. Through a Research Infrastructure Award from AES and competitive administrative supplements from NINDS, funding ($200,000 total costs) has been secured for the key experiment. Comparisons of results between laboratories will be facilitated by using the NINDS/NIMH DNA Microarray facilities for the hybridiations, which should significantly reduce variability due to sample handling and processing. The major goal of the consortium is to identify gene expression profiles of dentate granule cells that are common to the early latent period of the four most widely used rat epilepsy models. These experiments are on-going.

Several other epilepsy researchers were awarded competitive administrative supplements in August of 2004 to look for changes in gene expression in their research areas.  These include: Chris Walsh, Jeff Noebels, Anne Anderson and Doug Coulter.  Their proposed experiments are on-going.

As of Thursday, Feb 3, 2005, epilepsy researchers Ray Dingledine, Sookyong Koh, Scott Thompson and Miklos Toth have used the NINDS/NIMH DNA Microarray Facility. 

Top priorities for next 5-10 years: 

Roadblocks to progress: 

References:

Becker AJ, Chen J, Zien A, Sochivko D, Normann S, Schramm J, Elger CE, Wiestler OD, Blumcke I. (2003) Correlated stage- and subfield-associated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy. Eur J Neurosci. 10:2792-802.

Bragin A, Karsten SL, Almajano J, Wilson CL, Geschwind DH, Engel J Jr. (2004)            Large-scale microarray gene expression analysis in discrete electrophysiologically identified neuronal clusters. J Neurosci Methods. 133:49-55.

Elliott RC, Miles MF, Lowenstein DH. (2003) Overlapping microarray profiles of dentate gyrus gene expression during development- and epilepsy-associated neurogenesis and axon outgrowth. J Neurosci. 23:2218-27.

Flood WD, Moyer RW, Tsykin A, Sutherland GR, Koblar SA.        (2004) Nxf and Fbxo33: novel seizure-responsive genes in mice. Eur J Neurosci. 7:1819-26.

Gu J, Lynch BA, Anderson D, Klitgaard H, Lu S, Elashoff M, Ebert U, Potschka H, Loscher W. (2004) The antiepileptic drug levetiracetam selectively modifies kindling-induced alterations in gene expression in the temporal lobe of rats. Eur J Neurosci. 19:334-45.

Hekmat-Scafe DS, Dang KN, Tanouye MA. (2005) Seizure-suppression by gain-of-function Escargot mutations. Genetics. [Epub ahead of print]

Lahteinen S, Pitkanen A, Knuuttila J, Toronen P, Castren E. (2004) Brain-derived neurotrophic factor signaling modifies hippocampal gene expression during epileptogenesis in transgenic mice. Eur J Neurosci. 12:3245-54.

Liu W, Seto J, Sibille E, Toth M. (2003) The RNA binding domain of Jerky consists of tandemly arranged helix-turn-helix/homeodomain-like motifs and binds specific sets of mRNAs. Mol Cell Biol. 12:4083-93.

Miyata H, Chiang AC, Vinters HV. (2004) Insulin signaling pathways in cortical dysplasia and TSC-tubers: tissue microarray analysis. Ann Neurol. 56:510-9.

Noh HS, Lee HP, Kim DW, Kang SS, Cho GJ, Rho JM, Choi WS. (2004) A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet. Brain Res Mol Brain Res. 129:80-7.

Telfeian AE, Tseng HC, Baybis M, Crino PB, Dichter MA. (2003) Differential expression of GABA and glutamate-receptor subunits and enzymes involved in GABA metabolism between electrophysiologically identified hippocampal CA1 pyramidal cells and interneurons. Epilepsia. 2:143-9.

Wang P, Saraswati S, Guan Z, Watkins CJ, Wurtman RJ, Littleton JT. (2004) A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase disrupts ATP generation and alters synaptic function. J Neurosci. 24:4518-29.

Wilson DN, Chung H, Elliot R, Bremer D, George D. Koh S, (2005) Microarray analysis of postictal transcriptional regulation of neuropeptides; J Mol Neurosci, 25:285-98.

Last updated January 12, 2010