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Icariin ameliorates learning and memory function via improving cerebral glucose metabolism disorder in APP/PS1/Tau triple transgenic Alzheimer's disease mice
Author(s) -
Jin Feng,
Zhang Ying,
Nie Jing,
Shi Jingshan
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.806.18
Subject(s) - icariin , morris water navigation task , endocrinology , medicine , hippocampus , epimedium , western blot , glut1 , glut3 , glucose transporter , carbohydrate metabolism , neun , genetically modified mouse , dentate gyrus , retrosplenial cortex , chemistry , transgene , biochemistry , insulin , pathology , immunohistochemistry , traditional chinese medicine , gene , alternative medicine
OBJECTIVE To investigate whether icariin (ICA), a flavonoid extracted from the Chinese herb ( Berberidaceae epimedium L), can ameliorate learning and memory function via improving cerebral glucose metabolism disorder in APP/PS1/Tau triple transgenic Alzheimer's disease mice (3×Tg‐AD mice). METHODS Three‐month‐old male 3×Tg‐AD mice were randomly divided into three groups (n=10 per group): 3×Tg group, 3×Tg + ICA 30 mg/kg group, 3×Tg + ICA 60 mg/kg group, and age‐matched male wild type (WT) mice were randomly divided into two groups (n=10 per group): WT control group, WT+ ICA 60 mg/kg group. ICA in vehicle (0.5% Tween‐80 in distilled water) was given orally once a day for five months in the 3×Tg+ICA groups, 3×Tg and WT control groups were given an equal volume vehicle. Morris water maze was used to detect the learning and memory function of mice. Brain glucose metabolism in 3×Tg‐AD mice was observed by 18F‐FDG microPET imaging technique. Nissl staining and HE staining were used to evaluate the survival neurons in hippocampus of mice. Glucose oxidase assay was used to detect glucose contents in cortex of mice. The protein expression of APP, Aβ 1‐40 , Aβ 1‐42 , glucose transporter 1 (GLUT1) and GLUT3, and the phosphorylation level of tau protein at multiple sites in hippocampus were detected by Western Blot. RESULTS Behavioral examination revealed a profound decrease learning and memory function, accompanied by a decrease in number of neuronal cells in 3×Tg‐AD mice. Moreover, the cerebral 18F‐FDG uptake rate per gram tissue was reduced, the glucose contents in the hippocampus and cortex were increased in 3×Tg‐AD mice. In addition, Western blot analysis showed that the expression of APP, Aβ 1‐40 , Aβ 1‐42 proteins and the levels of tau protein phosphorylation at Ser199/202 and PHF‐1 (Ser396/404) sites were increased significantly, followed by a decrease of GLUT1 and GLUT3 expression in hippocampus of 3×Tg‐AD mice. All of these changes in behavioral functions, 18F‐FDG uptake rate, glucose contents, neuronal loss and the related protein expression were reversed when mice were treated with ICA. CONCLUSION ICA can improve the learning and memory ability of AD model mice, the mechanism may be related to the improvement of cerebral glucose metabolism dysfunction by increasing the expression of GLUT. Support or Funding Information This work was supported by the National Natural Science Foundation of China (81660599), the Foundation of Zunyi Medical University (2013F‐686, F‐738), The Postgraduate Education Foundation of Guizhou Province (KYJJ2017008). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .