title: Injection of Aβ1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew.
abstract: Alzheimer's disease (AD) can incur significant health care costs to the patient, their families, and society; furthermore, effective treatments are limited, as the mechanisms of AD are not fully understood. This study utilized twelve adult male tree shrews (TS), which were randomly divided into PBS and amyloidbetapeptide1-40 (Aβ1-40) groups. AD model was established via an intracerebroventricular (icv) injection of Aβ1-40 after being incubated for 4 days at 37 °C. Behavioral, pathophysiological and molecular changes were evaluated by hippocampal-dependent tasks, magnetic resonance imaging (MRI), silver staining, hematoxylin-eosin (HE) staining, TUNEL assay and gene sequencing, respectively. At 4 weeks post-injection, as compared with the PBS group, in Aβ1-40 injected animals: cognitive impairments happened, and the hippocampus had atrophied indicated by MRI findings; meanwhile, HE staining showed the cells of the CA3 and DG were significantly thinner and smaller. The average number of cells in the DG, but not the CA3, was also significantly reduced; furthermore, silver staining revealed neurotic plaques and neurofibrillary tangles (NFTs) in the hippocampi; TUNEL assay showed many cells exhibited apoptosis, which was associated with downregulated BCL-2/BCL-XL-associated death promoter (Bad), inhibitor of apoptosis protein (IAP), Cytochrome c (CytC) and upregulated tumor necrosis factor receptor 1 (TNF-R1); lastly, gene sequencing reported a total of 924 mobilized genes, among which 13 of the downregulated and 19 of the upregulated genes were common to the AD pathway. The present study not only established AD models in TS, but also reported on the underlying mechanism involved in neuronal apoptosis associated with multiple gene expression.
authors.affiliation: Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming, 650031, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Liu-Lin
authors.initials: LL
authors.lastname: Xiong
authors.affiliation: Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming, 650031, China.
authors.forename: Rong-Ping
authors.initials: RP
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming, 650031, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming, 650031, China.
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Qian
authors.affiliation: Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming, 650031, China.
authors.forename: Piao
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming, 650500, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Fa-Bao
authors.initials: FB
authors.lastname: Gao
authors.affiliation: Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming, 650031, China. tinghua_neuron@263.net.|Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China. tinghua_neuron@263.net.|Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming, 650500, China. tinghua_neuron@263.net.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007267:Injections; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage; D014418:Tupaiidae
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)
keywords: Alzheimer disease; Apoptosis; Cognitive function; Gene sequencing; MRI