PMID- 11925568
OWN - NLM
STAT- MEDLINE
DCOM- 20020502
LR  - 20231213
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 30
IP  - 4
DP  - 2002 Apr
TI  - c-fos regulates neuronal excitability and survival.
PG  - 416-20
AB  - 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.
FAU - Zhang, Jianhua
AU  - Zhang J
AD  - Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati 
      College of Medicine, Cincinnati, Ohio 45267, USA.
FAU - Zhang, Dongsheng
AU  - Zhang D
FAU - McQuade, Jill Slane
AU  - McQuade JS
FAU - Behbehani, Michael
AU  - Behbehani M
FAU - Tsien, Joe Z
AU  - Tsien JZ
FAU - Xu, Ming
AU  - Xu M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020304
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Receptors, Kainic Acid)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Death
MH  - Cell Nucleus/metabolism
MH  - Cell Survival
MH  - Electroencephalography
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Gene Expression Regulation
MH  - Genes, fos/*genetics
MH  - Genotype
MH  - Hippocampus/metabolism
MH  - Immunohistochemistry
MH  - Kainic Acid/pharmacology
MH  - Mice
MH  - Models, Genetic
MH  - Mutation
MH  - Neurons/*metabolism
MH  - Nucleic Acid Hybridization
MH  - Proto-Oncogene Proteins c-fos/*physiology
MH  - Receptors, Kainic Acid/biosynthesis
MH  - Time Factors
MH  - Transfection
MH  - GluK2 Kainate Receptor
EDAT- 2002/04/02 10:00
MHDA- 2002/05/03 10:01
CRDT- 2002/04/02 10:00
PHST- 2002/04/02 10:00 [pubmed]
PHST- 2002/05/03 10:01 [medline]
PHST- 2002/04/02 10:00 [entrez]
AID - ng859 [pii]
AID - 10.1038/ng859 [doi]
PST - ppublish
SO  - Nat Genet. 2002 Apr;30(4):416-20. doi: 10.1038/ng859. Epub 2002 Mar 4.