title: Neurogenic responses to amyloid-beta plaques in the brain of Alzheimer's disease-like transgenic (pPDGF-APPSw,Ind) mice.
abstract: Formation and accumulation of amyloid-beta (A beta) plaques are associated with declined memory and other neurocognitive function in Alzheimer's disease (AD) patients. However, the effects of A beta plaques on neural progenitor cells (NPCs) and neurogenesis from NPCs remain largely unknown. The existing data on neurogenesis in AD patients and AD-like animal models remain controversial. For this reason, we utilized the nestin second-intron enhancer controlled LacZ (pNes-LacZ) reporter transgenic mice (pNes-Tg) and Bi-transgenic mice (Bi-Tg) containing both pPDGF-APPSw,Ind and pNes-LacZ transgenes to investigate the effects of A beta plaques on neurogenesis in the hippocampus and other brain regions of the AD-like mice. We chose transgenic mice at 2, 8 and 12 months of age, corresponding to the stages of A beta plaque free, plaque onset and plaque progression to analyze the effects of A beta plaques on the distribution and de novo neurogenesis of (from) NPCs. We demonstrated a slight increase in the number of NPCs in the hippocampal regions at the A beta plaque free stage, while a significant decrease in the number of NPCs at A beta plaque onset and progression stages. On the other hand, we showed that A beta plaques increase neurogenesis, but not gliogenesis from post-mitotic NPCs in the hippocampus of Bi-Tg mice compared with age-matched control pNes-Tg mice. The neurogenic responses of NPCs to A beta plaques suggest that experimental approaches to promote de novo neurogenesis may potentially improve neurocognitive function and provide an effective therapy for AD.
authors.affiliation: Department of Anatomy and Cell Biology, University of North Dakota School of Medicine, Grand Forks, ND 58202, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.forename: Shuhong
authors.initials: S
authors.lastname: Qiao
authors.forename: Xun
authors.initials: X
authors.lastname: Lan
authors.forename: Liying
authors.initials: L
authors.lastname: Chi
authors.forename: Chun
authors.initials: C
authors.lastname: Luo
authors.forename: Lindsey
authors.initials: L
authors.lastname: Lien
authors.forename: Qing
authors.initials: Q
authors.lastname: Yan Liu
authors.forename: Rugao
authors.initials: R
authors.lastname: Liu
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D058225:Plaque, Amyloid / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D010982:Platelet-Derived Growth Factor; D001616:beta-Galactosidase; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine