title: Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment.
abstract: Deficits in the Notch pathway are involved in a number of neurologic diseases associated with mental retardation or/and dementia. The mechanisms by which Notch dysregulation are associated with mental retardation and dementia are poorly understood. We found that Notch1 is highly expressed in the adult-born immature neurons in the hippocampus of mice. Retrovirus mediated knockout of notch1 in single adult-born immature neurons decreases mTOR signaling and compromises their dendrite morphogenesis. In contrast, overexpression of Notch1 intracellular domain (NICD), to constitutively activate Notch signaling in single adult-born immature neurons, promotes mTOR signaling and increases their dendrite arborization. Using a unique genetic approach to conditionally and selectively knockout notch 1 in the postnatally born immature neurons in the hippocampus decreases mTOR signaling, compromises their dendrite morphogenesis, and impairs spatial learning and memory. Conditional overexpression of NICD in the postnatally born immature neurons in the hippocampus increases mTOR signaling and promotes dendrite arborization. These data indicate that Notch signaling plays a critical role in dendrite development of immature neurons in the postnatal brain, and dysregulation of Notch signaling in the postnatally born neurons disrupts their development and thus contributes to the cognitive deficits associated with neurological diseases.
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.|Department of Cognitive sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Ding
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xin-Chun
authors.initials: XC
authors.lastname: Ding
authors.affiliation: Department of Cognitive sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D003712:Dendrites / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D019426:Integrases / Q000378:metabolism; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology*; D018345:Mice, Knockout; D055495:Neurogenesis; D009473:Neuronal Plasticity; D000072417:Protein Domains; D051881:Receptor, Notch1 / Q000737:chemistry / Q000378:metabolism*; D012190:Retroviridae / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction; D065852:Spatial Memory; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D051881:Receptor, Notch1; D038601:Ribosomal Protein S6; C448579:ribosomal protein S6, mouse; D058570:TOR Serine-Threonine Kinases; C045073:Cre recombinase; D019426:Integrases