The mechanism study of EGCG on improvement of cognitive function and alleviation of hippocampal insulin resistance in APP/PS 1 transgenetic mice

Objective To explore mechanism of epigallocatechin-3-gallate(EGCG) on improvement of cognitive function and alleviation of hippocampal insulin resistance in APP/PS 1 transgenetic mice.Method 12 months old female APP/PS 1 mice were randomly divided into 3 groups:model group(Tg),EGCG low dose group(Tg /EGCG-L),high dose group(Tg /EGCG-H).C 57 BL/6 J mice were utilized as control,learning and memory ability in 4 group mice were detected by morris water maze test(MWM).The hippocampal TNF-α/JNK signal and IRS-1 pSer 312 expression were detected by Western blot and immunohistochemical staining.Results Compared with NT mice,Tg mice showed a marked prolongation of the escape latency and swimming distance in the MWM test(P0.05);Abnormal activation of TNF-α/JNK signaling and increased IRS-1 pSer 312expression in the hippocampus of Tg mice(P0.05).EGCG-treated Tg mice showed significantly improvement of all these abnormal changes(P0.05).Conclusion EGCG treatment is able to alleviate hippocampal insulin resistance and improve cognitive function in the APP/PS 1 mice,which may be partly attributed to the reduction of TNF-α/JNK signaling activity in this AD mouse model.