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CJAP ›› 2018, Vol. 34 ›› Issue (5): 389-395.doi: 10.12047/j.cjap.5656.2018.089

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The improvement effect of scFv17 on the gait of triple-transgenic mice

WANG Ting, CAO Yue, HU Meng-ming, ZHANG Xiu-min, DONG Xue-fan, QI Jin-shun, ZHANG Jun, YANG Wei   

  1. Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China
  • Received:2017-11-27 Revised:2018-07-28 Online:2018-09-28 Published:2019-02-21
  • Supported by:

Abstract: Objective: To observe the gait changes of Alzheimer's disease PS1M146V/APPswe/tauP301L triple-transgenic (3xTg-AD) mice and to investigate the improvement effect of single chain variable domain antibody fragment 17 (scFv17) on the gait.Methods: In the present study, a selection of 6-month-old 3xTg-AD mice (n=18) and C57BL/6 wild-type mice (n=24) was performed. First, we observed their gait changes and found that the gait of 12-month-old 3xTg-AD mice was severely damaged. Then, the two groups of mice were randomly divided into four groups:WT+PBS(n=12), WT+scFv17(n=12), 3xTg-AD+PBS(n=9) and 3xTg-AD+scFv17(n=9). The gait behavior test and pathological test were performed after 12 weeks'continuous administration of scFv17 (1.5 mg/kg) or an equal volume of PBS (0.01 mol/L) by nasal gavage twice a week. Results: Compared with the same month old wild type mice, the rear track width of 12 month old 3xTg-AD mice was increased(P<0.01), swing time percent was decreased (P<0.01), stance time percent was increased(P<0.01), so the ability of movement coordination and balance was seriously damaged. ScFv17 could improve the coordination and balance ability of 12 month old 3xTg-AD mice(P<0.01). The morphological structure of 3xTg-AD mice cerebellar Purkinje cells was improved. The treatment of scFv17 increased the Nissl body number of the cerebellar Purkinje cells of 3xTg-AD mice (P<0.01). scFv17 reduced the amyloid β protein (Aβ) plaques in the cerebellar cortex of 3xTg-AD mice (P<0.01), and scFv17 reduced the intracellular neurofibrillary tangles (NFT) of the cerebellar Purkinje cells of the 3xTg-AD mice (P<0.01). Conclusion: The coordination and balance ability of 3xTg-AD mice was significantly impaired. ScFv17 can improve gait behaviour in the 3xTg-AD significantly.The mechanism may be related to the improvement of the structure and protein function of cerebellar Purkinje cells, and the eliminating of the Aβ plaques and the neurofibrillary tangles.

Key words: 3xTg-AD mice, gait, cerebellum, scFv17

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