title: Notch1 mediates postnatal neurogenesis in hippocampus enhanced by intermittent hypoxia.
abstract: Notch1 is a transcription factor on the membrane and regulates various stages of neurogenesis. Recently, studies have shown that in vitro neurogenesis is enhanced by hypoxia, and there is cross-coupling between Notch and hypoxia signaling pathways in vitro. However, to date, no data have reported whether Notch1 can be regulated by hypoxia in vivo and mediates hypoxia-induced neurogenesis. To determine causative links between Notch1, neurogenesis and hypoxia, we examined multiple steps of hippocampal neurogenesis followed intermittent hypoxia (IH) in wild type (WT) and Notch1 heterozygous deficient (N+/-) mice. We found that IH increased NSC proliferation, newborn neuron survival and migration, and spine morphogenesis in dentate gyrus of hippocampus, as well as neurogenesis in olfactory bulb in WT mice. However, IH-enhanced neurogenesis was inhibited in N+/- mice. It was shown that Notch1 signaling was activated following IH in WT mice, but not in N+/- mice. Our data indicated that IH, as a novel external stimulus, enhances neurogenesis at multiple stages and that Notch1 is activated by hypoxia in vivo and required for hypoxia-induced neurogenesis. These results suggest IH as a novel therapeutic strategy for degenerative neurological disorders and provide evidence for causative links between Notch1, neurogenesis and hypoxia.
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China; Brain Research Center, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Kuiwu
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: linglingzhu@hotmail.com.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Zhu
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: fanming@nic.bmi.ac.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C497762:Notch1 protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1
keywords: Dentate gyrus; Mouse; Neural stem cell; Oxygen