The remodeling of neuronal circuits that develop in many types of epilepsy is thought to involve altered transcriptional activity and subsequent gene expression during epileptogenesis. Gene expression profiles are altered in epilepsy but the transcriptional regulatory mechanisms underlying these changes in epilepsy are not defined. The specific transcriptional regulator, nuclear factor-kappa B (NF-KappaB) has been identified as a potential key regulator of gene responses in epilepsy. We have pilot data suggesting that NF-KappaB activation correlates with acute seizures and the development of chronic epilepsy in the kainate model. Therefore, I propose to characterize NF-KB activation and transcriptional regulation of NF-KB responsive genes in the kainate epilepsy model and determine if NF-KappaB contributes to the epileptic phenotype. We anticipate that the proposed studies will help to further characterize the cellular and molecular mechanisms by which NF-KappaB is activated in epilepsy and to determine whether NF-KappaB contributes to altered gene expression in epilepsy. Investigations into the mechanisms involved in NF-KappaB activation in hippocampus will provide insights into the role of this transcription factor in epileptogenesis and possibly the maintenance of the epileptic circuitry. These studies may also identify novel targets for therapeutics in epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS048811-01A1
Application #
6885086
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Jacobs, Margaret
Project Start
2004-12-14
Project End
2007-12-13
Budget Start
2004-12-14
Budget End
2005-12-13
Support Year
1
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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