Effects of Semaglutide on cognitive function in transgenic APP/PS1/tau mice
Objective To explore whether Semaglutide can effectively improve the cognitive function of amyloid precursor protein(APP)/presenilin-1(PS1)/microtubule-associated protein tau(tau)transgenic mice with Alzheimer's disease(AD).Methods AD model mice with three gene mutation sites,PS1M146V,APPSwe,and tauP301L,that is,APP/PS1/Tau triple transgenic AD mice(3 xTg-AD)were selected for this study.Seven-month-old APP/PS1/tau triple transgenic mice and non-transgenic wild type(WT)C57BL/6 littermates were respectively randomized into AD model group(Tg)and Semaglutide group(Tg+Semaglutide),and normal control group(WT)and Semaglutide control group(WT+Semaglutide).Mice in WT+Semaglutide group and Tg+Semaglutide group were intraperitoneally injected with Semaglutide,and mice in WT group and Tg group were intraperitoneally injected with equal amounts of normal saline.The intervention was performed once two days for 30 times.After the intervention,the novel object recogni-tion test was conducted to study the changes in the cognitive function of mice.The enzyme-linked immunosorbent assay(ELISA)was conducted to detect the serum levels of cognition-related marker Aβ1-42 in mice.Western blot method was used to detect the expression of phosphorylated Tau protein at the Ser231 site in the hippocampus of mice.Results In novel object recognition test,the new object discrimination ratio in Tg+Semaglutide group was higher than that in Tg group(P＜0.05),and the new object discrimination ratio in WT+Semaglutide group was higher than that in WT group(P＜0.05).After the intervention(9 months old),there was no sig-nificant difference in body mass and blood glucose concentration among all groups(P＞0.05).Western blot experiments showed that the phosphorylation level of Tau231 was lower in Tg+Semaglutide group than in Tg group(P＜0.05),while the phosphorylation level of Tau231 was also slightly lower in WT+Semaglutide group than in WT group,but there was no significant difference between two groups.ELISA results showed that the concentration of Aβ1-42 was significantly lower in Tg+Semaglutide group than in Tg group(P＜0.05),and the concentration of Aβ1-42 was lower in WT+Semaglutide group than in WT group(P＜0.05).Conclusion Semaglutide can reduce the level of cognition-related marker Aβ1-42 and inhibit the expression of phosphorylated Tau protein at the Ser231 site in the hippocampus,thus effectively improving the cognitive function of AD mice.In addition,Semaglutide has no significant effect on body mass and blood glucose concentration of mice in a short period,suggesting its high security.
SemaglutideAlzheimer's diseaseTau protein phosphorylationAPP/PS1/tau triple transgenic miceAβ1-42type 2 diabetes mellitus
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