c-fos regulates neuronal excitability and survival

Jianhua Zhang, Dongsheng Zhang, Jill Slane McQuade, Michael Behbehani, Joseph Zhuo Tsien, Ming Xu

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

Excitotoxicity is a process in which glutamate or other excitatory amino acids induce neuronal cell death. Accumulating evidence suggests that excitotoxicity may contribute to human neuronal cell loss caused by acute insults and chronic degeneration in the central nervous system1-4. The immediate early gene (IEG) c-fos encodes a transcription factor5-6. The c-Fos proteins form heterodimers with Jun family proteins, and the resulting AP-1 complexes regulate transcription by binding to the AP-1 sequence found in many cellular genes7-9. Emerging evidence suggests that c-fos is essential in regulating neuronal cell survival versus death10. Although c-fos is induced by neuronal activity, including kainic acid-induced seizures11-14, whether and how c-fos is involved in excitotoxicity is still unknown. To address this issue, we generated a mouse in which c-fos expression is largely eliminated in the hippocampus. We found that these mutant mice have more severe kainic acid-induced seizures, increased neuronal excitability and neuronal cell death, compared with control mice. Moreover, c-Fos regulates the expression of the kainic acid receptor GluR6 and brain-derived neurotrophic factor (BDNF), both in vivo and in vitro. Our results suggest that c-fos is a genetic regulator for cellular mechanisms mediating neuronal excitability and survival.

Original languageEnglish (US)
Pages (from-to)416-420
Number of pages5
JournalNature Genetics
Volume30
Issue number4
DOIs
StatePublished - Jan 1 2002

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Kainic Acid
Transcription Factor AP-1
Survival
Cell Death
Proto-Oncogene Proteins c-fos
Kainic Acid Receptors
Excitatory Amino Acids
Immediate-Early Genes
Brain-Derived Neurotrophic Factor
Glutamic Acid
Hippocampus
Cell Survival
Seizures
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Genetics

Cite this

Zhang, J., Zhang, D., McQuade, J. S., Behbehani, M., Tsien, J. Z., & Xu, M. (2002). c-fos regulates neuronal excitability and survival. Nature Genetics, 30(4), 416-420. https://doi.org/10.1038/ng859

c-fos regulates neuronal excitability and survival. / Zhang, Jianhua; Zhang, Dongsheng; McQuade, Jill Slane; Behbehani, Michael; Tsien, Joseph Zhuo; Xu, Ming.

In: Nature Genetics, Vol. 30, No. 4, 01.01.2002, p. 416-420.

Research output: Contribution to journalArticle

Zhang, J, Zhang, D, McQuade, JS, Behbehani, M, Tsien, JZ & Xu, M 2002, 'c-fos regulates neuronal excitability and survival', Nature Genetics, vol. 30, no. 4, pp. 416-420. https://doi.org/10.1038/ng859
Zhang J, Zhang D, McQuade JS, Behbehani M, Tsien JZ, Xu M. c-fos regulates neuronal excitability and survival. Nature Genetics. 2002 Jan 1;30(4):416-420. https://doi.org/10.1038/ng859
Zhang, Jianhua ; Zhang, Dongsheng ; McQuade, Jill Slane ; Behbehani, Michael ; Tsien, Joseph Zhuo ; Xu, Ming. / c-fos regulates neuronal excitability and survival. In: Nature Genetics. 2002 ; Vol. 30, No. 4. pp. 416-420.
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