The improvement effect of scFv17 on the gait of triple-transgenic mice.
10.12047/j.cjap.5656.2018.089
- Author:
Ting WANG
1
;
Yue CAO
1
;
Meng-Ming HU
1
;
Xiu-Min ZHANG
1
;
Xue-Fan DONG
1
;
Jin-Shun QI
1
;
Jun ZHANG
1
;
Wei YANG
1
Author Information
1. Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
- Publication Type:Journal Article
- Keywords:
3xTg-AD mice;
cerebellum;
gait;
scFv17
- MeSH:
Alzheimer Disease;
Amyloid beta-Peptides;
Amyloid beta-Protein Precursor;
Animals;
Disease Models, Animal;
Gait;
Mice;
Mice, Inbred C57BL;
Mice, Transgenic;
tau Proteins
- From:
Chinese Journal of Applied Physiology
2018;34(5):389-395
- CountryChina
- Language:Chinese
-
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 (=18) and C57BL/6 wild-type mice (=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(=12), WT+scFv17(=12), 3xTg-AD+PBS(=9) and 3xTg-AD+scFv17(=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(<0.01), swing time percent was decreased (<0.01), stance time percent was increased(<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(<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 (<0.01). scFv17 reduced the amyloid β protein (Aβ) plaques in the cerebellar cortex of 3xTg-AD mice (<0.01), and scFv17 reduced the intracellular neurofibrillary tangles (NFT) of the cerebellar Purkinje cells of the 3xTg-AD mice (<0.01).
CONCLUSIONS: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.
