2002
DOI: 10.1038/ng859
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c-fos regulates neuronal excitability and survival

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 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 … Show more

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Cited by 278 publications
(204 citation statements)
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“…In contrast, upregulation of BDNF by exercise 25,40,41 or by other in vitro manipulations leads to induction of these genes. 48 IEG induction is known to be strongly regulated via the MEK-ERK pathway, 49,50 which is also one of the main effectors of BDNF signaling. 51,52 Hence, we propose that the IEG transcript downregulations we see in the BDNF-deficient animals are due to the lack of release of BDNF and impaired trophic support.…”
Section: Discussionmentioning
confidence: 99%
“…In contrast, upregulation of BDNF by exercise 25,40,41 or by other in vitro manipulations leads to induction of these genes. 48 IEG induction is known to be strongly regulated via the MEK-ERK pathway, 49,50 which is also one of the main effectors of BDNF signaling. 51,52 Hence, we propose that the IEG transcript downregulations we see in the BDNF-deficient animals are due to the lack of release of BDNF and impaired trophic support.…”
Section: Discussionmentioning
confidence: 99%
“…This is the first study to investigate alterations in c-Fos expression resulting from sub-lethal HAB toxin exposure in an ecologically relevant fish species. These resulting alterations may serve to compromise or enhance the survival of exposed animals (Zhang et al, 2002), including exposed killifish and other estuarine species. Ultimately, this study shows that alterations in c-Fos expression provides a sensitive measure of low-level HAB stress exposure in fish.…”
Section: Discussionmentioning
confidence: 99%
“…IEG activation then codes for new proteins such as cytokines, enzymes, HSP70, as well as transcription factors leading to neuronal phenotypic changes (Herrera and Robertson, 1996). These phenotypic changes alter gene expression through the dimerization of c-Fos and AP-1 complex binding (Herdegen and Leah, 1998;Bakin and Curran, 1999;Zhang et al, 2002;Hansson et al, 2003). As a result, c-Fos induction can be used as a biomarker of neuronal and regional brain activity when animals are exposed to different types of stressful stimuli (Martinez et al, 2002;Rybnikova et al, 2003).…”
Section: Introductionmentioning
confidence: 99%
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“…Both receptors are highly prevalent and co-expressed in the majority of the hippocampal neurons (Cintra et al, 1994;Van Eekelen and De Kloet, 1992). Emerging evidence suggests that the inducible transcription factor and immediate early gene (IEG) c-Fos is essential for neuronal cell survival through its regulation of downstream genes such as BDNF (Zhang et al, 2002). The expression of c-fos and the IEG early growth response gene (egr-1, alternatively known as zif268, krox24, NGFI-A or TIS8) have both been used as functional markers of brain activity and neuroplasticity (James et al, 2005;Pfenning et al, 2007;Sheng and Greenberg, 1990).…”
Section: Introductionmentioning
confidence: 99%