Tau Protein Abnormal Phosphorylation Of Hippocampus By Excessive Activation Of MTOR Signaling Pathway In Diabetic Mice

OBJECTIVES:Study the connection of mTOR signaling pathway (p-mTOR and p-p70S6K) and Tau protein hyperphosphorylation on the diabetic mices induced by STZ(streptozocin, STZ).METHODS:Male C57BL/6J mice were divided into two groups randomly as follows:normal control group(Con group,n=10), diabetic group(n=40).After adaptive feeding for one week,Diabetes group was induced by intraperitoneal injection of STZ (200mg/kg), tail vein blood glucose was measured after48hours, and the mices whose blood glucose were more than16.7mmol/1were the successful modeling (n=38);the Con group (n=10) mices were injected with the same amount of citric acid buffer. After eatablish the model successfully, the diabetes group were randomly divided into two groups, diabetic control group (DM group,n=20),diabetes rapamycin intervention group(Rap group,n=20). The Rap Group mices were given intraperitoneal injection rapamycin solution (2000ul/kg,2.5mg rapamycin powder was dissolved in2000ul DMSO solution) of once a day. The DM group and the Con group were given the same amount of DMSO solution by intraperitoneal injection once a day. After15days of drug intervention,part of the mices Blood was collected for measurement of blood glucose before the animals were decapitated.Left and right hippocampus were preserved by liquid nitrogen, in order to extract the hippocampus protein for taking Western bloting of p-mTOR,p-p70S6K,p-Tau,mices lefted were perfused with4%neutral formalin and taken brain, hippocampus from each group were processed for routine paraffin embedding. Paraffin-embedded sections were cut throughout the tissue and processed with immunohistochemical.RESULTS:(1)HE staining showed that:The hippocampus of Con group was integrity, Pyramidal cells were arranged in neat, compact and morphology normal,but the cells in the DM and Rap group were disorder, disruption and decreased.(2)Immunohistochemical showed that: Compared with the Con group, expression of p-Tau(Ser396) was increased in hippocampus of the DM group;Compared with the DM group, the expression of p-Tau(Ser396) was reduced in hippocampus of the Rap group.(3) Compared with the Con group,the expression of p-Tau(Ser396) was increased in hippocampus of the DM group, the differences was statistically significant(P<0.05); Compared with the DM group, the expression of p-Tau(Ser396) was reduced in hippocampus of the Rap group, the differences was statistically significant(p <0.05);(4)Compared with the Con group,the expression of p-mTOR (Ser2448) and p-p70S6K(Thr421/Ser424) were increased in hippocampus of the DM group, the differences were statistically significant (p<0.05); Compared with the DM group, the expression of p-mTOR(Ser2448) and p-p70S6K (Thr421/Ser424) were reduced in hippocampus of the Rap group, the differences were statistically significant (p<0.05);CONCLUSIONS:Our research resulted that mTOR signaling pathway is excessive activate in the hippocampus of STZ-induced diabetic mice.Then by that it could make Tau protein abnormal phosphtorylate.