**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.