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.
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