title: Increased hippocampal neurogenesis in the progressive stage of Alzheimer's disease phenotype in an APP/PS1 double transgenic mouse model.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with senile beta-amyloid (Abeta) plaques and cognitive decline. Neurogenesis in the adult hippocampus is implicated in regulating learning and memory, and is increased in human postmortem brain of AD patients. However, little is currently known about the changes of hippocampal neurogenesis in the progression of AD. As brain tissues from patients during the progression of AD are generally not available, an amyloid precursor protein (APP)/presenilin1 (PS1) double transgenic mouse model of AD was studied. Bromodeoxyuridine (BrdU) labeling supported by doublecortin staining was used to detect proliferating hippocampal cells in the mice. Compared with age-matched wild-type controls, 9-month-old transgenic mice with memory impairment and numerous brain Abeta deposits showed increased numbers of proliferating hippocampal cells. However, 3-month-old transgenic mice with normal memory and subtle brain Abeta deposits showed normal hippocampal proliferation. Double immunofluorescent labeling with BrdU and either NeuN or glial fibrillary acidic protein was conducted in mice at 10 months (28 days after the last BrdU injection) to determine the differentiation of proliferating cells. The number of hippocampal BrdU-positive cells and BrdU-positive cells differentiating into neurons (neurogenesis) in 10-month-old mice was greater in transgenic mice compared with age-matched controls, but the ratio of hippocampal BrdU-positive cells differentiating into neurons and astroglia was comparable. These results suggest hippocampal neurogenesis may increase during the progression of AD. Targeting this change in neurogenesis and understanding the underlying mechanism could lead to the development of a new treatment to control the progression of AD.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Yu
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huanmin
authors.initials: H
authors.lastname: Luo
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Tou
authors.initials: T
authors.lastname: Zhao
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Huang
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D018450:Disease Progression; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009479:Neuropeptides; D009687:Nuclear Proteins; D053764:Presenilin-1; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C528900:glial fibrillary astrocytic protein, mouse