Effect of tenuigenin on tau protein phosphorylation at Ser~(396) site in neurons of AD rats induced by Aβ_(1-40)

AIM: To investigate the effect of tenuigenin(TEN) on hyperphosphorylation of tau protein in neurons of amyloid β-peptide1-40(Aβ1-40)-induced Alzheimer disease(AD) rats.METHODS: Aβ1-40 was injected into hippocampus CA1 region of the rats to establish AD model.TEN at different doses(18.5 mg/kg,37.0 mg/kg and 74.0 mg/kg) was intragastrically administered.The protein expression of protein kinase A(PKA),protein phosphatase 2A(PP2A),total tau and p-tau(Ser396) in the neurons was observed by the method of immunohistochemistry.The protein content of total tau and p-tau(Ser396),and the expression level of PKA and PP-2A were detected by Western blotting analysis.RESULTS: In Aβ1-40 group,the level of total tau,the phosphorylation of tau protein and the expression of PKA were significantly increased compared with those in sham operation group.Meanwhile,the expression of PP2A in Aβ1-40 group was lower than that in sham operation group.In TEN treatment group,the level of total tau,the phosphorylation of tau protein and the expression of PKA were markedly decreased,and the expression of PP2A was increased as compared with Aβ1-40 group.CONCLUSION: TEN may protect the neurons from the toxic effect of Aβ1-40 and reduce the hyperphosphorylation of tau(Ser396) in the neurons of AD rats by activating the expression of PP2A and inhibiting the expression of PKA.