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Injection of Aβ1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew.

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机构: [1]Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming 650031, China [2]Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China [3]Molecular Imaging Laboratory, Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China [4]Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming 650500, China
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摘要:
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.

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出版当年[2016]版:
大类 | 2 区 生物
小类 | 3 区 生化与分子生物学 3 区 细胞生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 3 区 细胞生物学
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第一作者机构: [1]Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming 650031, China
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通讯机构: [1]Institute of Neuroscience, Center of Experimental Animals, Kunming Medical University, Kunming 650031, China [2]Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China [4]Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming 650500, China
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