2013年4月
fosB-Null Mice Display Impaired Adult Hippocampal Neurogenesis and Spontaneous Epilepsy with Depressive Behavior
NEUROPSYCHOPHARMACOLOGY
- 巻
- 38
- 号
- 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
- ID情報
-
- DOI : 10.1038/npp.2012.260
- ISSN : 0893-133X
- eISSN : 1740-634X
- PubMed ID : 23303048
- Web of Science ID : WOS:000316161300018