title: Hippocampal neurogenesis in the APP/PS1/nestin-GFP triple transgenic mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is one of the most common causes of dementia. Although the exact mechanisms of AD are not entirely clear, the impairment in adult hippocampal neurogenesis has been reported to play a role in AD. To assess the relationship between AD and neurogenesis, we studied APP/PS1/nestin-green fluorescent protein (GFP) triple transgenic mice, a well-characterized mouse model of AD, which express GFP under the control of the nestin promoter. Different ages of AD mice and their wild-type littermates (WT) were used in our study. Immunofluorescent staining showed that neurogenesis occurred mainly in the subgranular zone (SGZ) of the dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles (LVs). The expression of neural stem cells (NSCs) (nestin) and neural precursors such as doublecortin (DCX) and GFAP in AD mice were decreased with age, as well as there being a reduction in 5-bromo-2-deoxyuridine (BrdU)-positive cells, when compared to WT. However, the number of maturate neurons (NeuN) was not significantly different between AD mice and wild-type controls, and NeuN changed only slightly with age. By Golgi-Cox staining, the morphologies of dendrites were observed, and significant differences existed between AD mice and wild-type controls. These results suggest that AD has a far-reaching influence on the regulation of adult hippocampal neurogenesis, leading to a gradual decrease in the generation of neural progenitors (NPCs), and inhibition of the differentiation and maturation of neurons.
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: M
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Anatomy, Chongqing Medical University, Chongqing 400016, China. Electronic address: guiqionghe@hotmail.com.
authors.forename: G
authors.initials: G
authors.lastname: He
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D049229:Dendritic Spines; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; C577485:Nes protein, mouse; D064231:Nestin; C508853:PSEN1 protein, human; D053764:Presenilin-1; D049452:Green Fluorescent Proteins
keywords: Alzheimer’s disease; hippocampal neurogenesis; neural progenitors; neurodegeneration