title: C-fos regulates neuropeptide Y expression in mouse dentate gyrus.
abstract: 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.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Wu
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Danwen
authors.initials: D
authors.lastname: Lou
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Fan
authors.forename: Bruce
authors.initials: B
authors.lastname: Aronow
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
mesh_terms: 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
chemical_list: D018690:Excitatory Amino Acid Agonists; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D007608:Kainic Acid