論文

査読有り
2013年4月

fosB-Null Mice Display Impaired Adult Hippocampal Neurogenesis and Spontaneous Epilepsy with Depressive Behavior

NEUROPSYCHOPHARMACOLOGY
  • Noriko Yutsudo
  • Takashi Kamada
  • Kosuke Kajitani
  • Hiroko Nomaru
  • Atsuhisa Katogi
  • Yoko H. Ohnishi
  • Yoshinori N. Ohnishi
  • Kei-ichiro Takase
  • Kunihiko Sakumi
  • Hiroshi Shigeto
  • Yusaku Nakabeppu
  • 全て表示

38
5
開始ページ
895
終了ページ
906
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/npp.2012.260
出版者・発行元
NATURE PUBLISHING GROUP

Patients with epilepsy are at high risk for major depression relative to the general population, and both disorders are associated with changes in adult hippocampal neurogenesis, although the mechanisms underlying disease onset remain unknown. The expression of fosB, an immediate early gene encoding FosB and Delta FosB/Delta 2 Delta FosB by alternative splicing and translation initiation, is known to be induced in neural progenitor cells within the subventricular zone of the lateral ventricles and subgranular zone of the hippocampus, following transient forebrain ischemia in the rat brain. Moreover, adenovirus-mediated expression of fosB gene products can promote neural stem cell proliferation. We recently found that fosB-null mice show increased depressive behavior, suggesting impaired neurogenesis in fosB-null mice. In the current study, we analyzed neurogenesis in the hippocampal dentate gyrus of fosB-null and fosB(d/d) mice that express Delta FosB/Delta 2 Delta FosB but not FosB, in comparison with wild-type mice, alongside neuropathology, behaviors, and gene expression profiles. fosB-null but not fosB(d/d) mice displayed impaired neurogenesis in the adult hippocampus and spontaneous epilepsy. Microarray analysis revealed that genes related to neurogenesis, depression, and epilepsy were altered in the hippocampus of fosB-null mice. Thus, we conclude that the fosB-null mouse is the first animal model to provide a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, fosB. Neuropsychopharmacology (2013) 38, 895-906; doi: 10.1038/npp.2012.260; published online 16 January 2013

リンク情報
DOI
https://doi.org/10.1038/npp.2012.260
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23303048
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000316161300018&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/npp.2012.260
  • ISSN : 0893-133X
  • eISSN : 1740-634X
  • PubMed ID : 23303048
  • Web of Science ID : WOS:000316161300018

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