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Apoptosis

, Volume 21, Issue 5, pp 621–640 | Cite as

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

  • Na Lin
  • Liu-Lin Xiong
  • Rong-ping Zhang
  • Hong Zheng
  • Lei Wang
  • Zhong-Yi Qian
  • Piao Zhang
  • Zhi-wei Chen
  • Fa-Bao Gao
  • Ting-Hua WangEmail author
Article

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.

Keywords

Alzheimer disease Cognitive function MRI Apoptosis Gene sequencing 

Supplementary material

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Supplementary material 1 (TIF 1798 kb)
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Supplementary material 2 (TIF 4497 kb)
10495_2016_1227_MOESM3_ESM.docx (35 kb)
Supplementary material 3 (DOCX 34 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Na Lin
    • 1
  • Liu-Lin Xiong
    • 2
  • Rong-ping Zhang
    • 1
  • Hong Zheng
    • 1
  • Lei Wang
    • 3
  • Zhong-Yi Qian
    • 1
  • Piao Zhang
    • 1
  • Zhi-wei Chen
    • 4
  • Fa-Bao Gao
    • 3
  • Ting-Hua Wang
    • 1
    • 2
    • 4
    Email author
  1. 1.Institute of Neuroscience, Center of Experimental AnimalsKunming Medical UniversityKunmingChina
  2. 2.Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China HospitalSichuan UniversityChengduChina
  3. 3.Molecular Imaging Laboratory, Department of Radiology, West China HospitalSichuan UniversityChengduChina
  4. 4.Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical EducationYunnan Normal UniversityKunmingChina

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