C-fos regulates neuropeptide Y expression in mouse dentate gyrus.
Excitotoxicity by which excitatory amino acid induces neuronal cell death may underlie mechanisms of neurodegenerative diseases. We previously found that c-fos is critically involved in neuronal excitability and survival. Mice that carry hippocampal mutations of c-fos exhibited hyper-excitability, hyper-excitotoxicity and higher mortality in kainic acid (KA)-induced seizures compared to wild-type mice. To further understand the neuroprotective signal transduction pathways regulated by c-fos in the hippocampal formation, we identified 172 genes that are either regulated by KA or are differentially expressed in wild-type and hippocampal-specific c-fos mutant mice using cDNA microarrays. One gene encodes the neuropeptide Y (NPY). We confirmed that c-fos regulates the expression of NPY by using immunohistochemistry. We found that c-fos is critical in up-regulation of NPY expression in the granule cell layer of dentate gyrus in response to KA administration. As NPY is an important endogenous anti-epileptic agent, our result is consistent with a hypothesis that the neuroprotective function of c-fos is mediated in part by regulation of NPY expression.
Wu
Yongfei
Y
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Zhang
Dongsheng
D
Lou
Danwen
D
Fan
Yunxia
Y
Aronow
Bruce
B
Xu
Ming
M
Zhang
Jianhua
J
D000818:Animals; D002452:Cell Count / Q000379:methods; D018891:Dentate Gyrus / Q000293:injuries / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D007608:Kainic Acid