(-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus
(-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus
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DOI：
10.1007/s11010-013-1675-x
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发表时间：
2013-08-01
影响因子：
4.3
通讯作者：
Cao, Yun-Peng
中科院分区：
文献类型：
--
作者：
Jia, Ning;Han, Kun;Cao, Yun-Peng
Alzheimer's disease (AD) fundamentally represents a metabolic disease associated with brain insulin resistance. TNF-alpha/c-Jun N-terminal kinase (JNK) signaling plays a central role in serine phosphorylation of insulin receptor substrate-1 (IRS-1). (-)-Epigallocatechin-3-gallate (EGCG), a potent antioxidant, has been verified to attenuate peripheral insulin resistance by reducing IRS-1 signaling blockage. This study aimed to investigate the effects and possible mechanisms of EGCG on central IRS-1 signaling in vivo. APP/PS1 mice were treated with EGCG, and spatial memory was assessed by the Morris water maze test. Levels of soluble and insoluble A beta 42 in the hippocampus were determined by ELISA. The activation of NF-alpha/JNK and IRS signaling was detected by immunohistochemistry and Western blot analysis. Our results showed that EGCG ameliorated the impaired learning and memory in APP/PS1 mice. Notably, we found a significant reduction of IRS-1pS636 level accompanied with decreased A beta 42 levels in the hippocampus of 13-month-old female APP/PS1 mice after treatment with EGCG (2 or 6 mg/kg/day) for 4 weeks. Furthermore, EGCG treatment inhibited TNF-alpha/JNK signaling and increased the phosphorylation of Akt and glycogen synthase kinase-3 beta in the hippocampus of APP/PS1 mice. In conclusion, our study provides evidence that long-term consumption of EGCG may alleviate AD-related cognitive deficits by effectively attenuating central insulin resistance.
