Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

c-fos regulates neuronal excitability and survival.

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 system. The immediate early gene (IEG) c-fos encodes a transcription factor. 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 genes. Emerging evidence suggests that c-fos is essential in regulating neuronal cell survival versus death. Although c-fos is induced by neuronal activity, including kainic acid-induced seizures, 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.

Pubmed ID: 11925568


  • Zhang J
  • Zhang D
  • McQuade JS
  • Behbehani M
  • Tsien JZ
  • Xu M


Nature genetics

Publication Data

April 1, 2002

Associated Grants


Mesh Terms

  • Animals
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor
  • Cell Death
  • Cell Nucleus
  • Cell Survival
  • Electroencephalography
  • Excitatory Amino Acid Agonists
  • Gene Expression Regulation
  • Genes, fos
  • Genotype
  • Hippocampus
  • Immunohistochemistry
  • Kainic Acid
  • Mice
  • Models, Genetic
  • Mutation
  • Neurons
  • Nucleic Acid Hybridization
  • Proto-Oncogene Proteins c-fos
  • Receptors, Kainic Acid
  • Time Factors
  • Transfection