Cellular and Molecular Neurobiology

, Volume 26, Issue 4, pp 383–403

CREB and NF-κB Transcription Factors Regulate Sensitivity to Excitotoxic and Oxidative Stress Induced Neuronal Cell Death

Article

DOI: 10.1007/s10571-006-9045-9

Cite this article as:
Zou, J. & Crews, F. Cell Mol Neurobiol (2006) 26: 383. doi:10.1007/s10571-006-9045-9

Summary

1. Glutamate–NMDA receptor excitotoxicity and oxidative stress are two common mechanisms associated with most neurodegenerative diseases. We hypothesize that the vital state of neurons is regulated in part by two key transcription factors, CREB and NF-κB. To test this hypothesis we used hippocampal–entorhinal cortex slice cultures.

2. Glutamate neurotoxicity and oxidative stress neurotoxicity, using hydrogen peroxide (H2O2) are both associated with a decrease in CREB DNA binding and an increase in NF-κB DNA binding.

3. Agents that modulate CREB and NF-κB DNA-binding activity alter neurotoxicity. Rolipram, a phosphodiesterase IV inhibitor, increased CREB DNA binding activity and decreased toxicity, whereas TNFα, increased NF-κB DNA-binding activity and increased neurotoxicity to both glutamate and H2O2. Ethanol decreased CREB and increased NF-κB DNA-binding activity and increased neurotoxicity to both glutamate and H2O2.

4. Brain-derived neurotrophic factor (BDNF) is a transcriptionally regulated trophic factor whose expression follows sensitivity to toxicity suggesting it is one of the transcriptionally regulated factors that contributes to neuronal vitality secondary to the balance of CREB–NF-κB-activated transcription. Together these studies suggest that neurotoxicity through glutamate–NMDA receptors or oxidative stress is dependent upon CREB and NF-κB DNA transcription that regulates vitality of neurons.

KEY WORDS:

CREB NF-κB glutamate oxidative stress TNFα ethanol slices 

Copyright information

© Springer Scinece+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.The Bowles Center For Alcohol StudiesDepartment of Pharmacology, School of Medicine, CB#7178, University of North Carolina at Chapel HillChapel HillUSA

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