首页|Effect of TSG on tau phosphorylation via GSK-3β pathway
Effect of TSG on tau phosphorylation via GSK-3β pathway
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Objective: To observe how TSG interferes with Tau phosphorylation in Aβ25-35 induced dementia model via GSK-3β pathway. Methods: Thirty-six male SD rats aged 24 months were randomly divided into control group, sham group, model group, low-dose, medium-dose and high-dose of TSG groups (TSG, 0.033, 0.1, 0.3g kg-1), with 6 rats in each group. Model group and TSG dose groups were injected Aβ25-35 into hippocampus by brain stereoscopic locator to induce dementia model (sham group was injected with equal volume of normal saline). Six SD rats of the same age were selected as normal group. 14d after modeling by Aβ25-35, the rats was given TSG by gavage. once A day in each group for 4 weeks. After 4 weeks of treatment with TSG, HE staining was used to observe the structural changes of nerve cells in brain tissue, IHC was used to observe the expression of PKC and PKA protein in brain tissue, real-time PCR was used to observe the mRNA expressions of GSK-3β, PKA, PI3K, PKB and PKC, and Western blot was used to observe the expression of GSK-3β, P-tau, PI3K and PKB protein in hippocampus. Results: Compared with normal group, the number of nerve cells in model group was less, and the arrangement was sparse and disordered. The expression of PI3K, PKB mRNA were significantly decrease(P<0.01), the expression of GSK-3β, PKA mRNA was go up(P<0.05), the exPression of PKC mRNA was decreased(P<0.05), the protein expression level of PKC(P<0.01), PI3K (P<0.05) and PKB(P<0.01)were decreased, the expression levels of PKC protein in hippocampus and cortex were significantly decreased(P<0.01), the expression levels of PKA protein in hippocampus and cortex were go up(P<0.05).Compared with model group, the number of nerve cells in each administration group increased to a certain extent, the expression levels of P-tau, GSK-3β and PKA protein and mRNA were significantly decrease(P<0.05, P<0.01), the expression levels of PI3K,PKB and PKC protein and mRNA were significantly up-regulated (P<0.05,P<0.01). Conclusion: TSG can regulate GSK-3β, PI3K, PKC, PKB and PKA in the hippocampus of Aβ25-35 induced dementia model. By regulating the expression of these factors, the hyperphosphorylation of Tau protein can be inhibited and the phenomenon of hyperphosphorylation of Tau protein can be improved.
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NSTL
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