(-)-Epigallocatechin-3-Gallate Ameliorates Learning and Memory Deficits by Adjusting the Balance of TrkA/p75NTR Signaling in APP/PS1 Transgenic Mice

被引：107

作者：

Liu, Mingyan ^{[1
]}

Chen, Fujun ^{[1
]}

Sha, Lei ^{[1
]}

Wang, Shuang ^{[1
]}

Tao, Lin ^{[1
]}

Yao, Lutian ^{[1
]}

He, Miao ^{[1
]}

Yao, Zhimin ^{[1
]}

Liu, Hang ^{[1
]}

Zhu, Zheng ^{[1
]}

Zhang, Zhenjie ^{[1
]}

Zheng, Zhihong ^{[2
]}

Sha, Xianzheng ^{[3
]}

Wei, Minjie ^{[1
]}

机构：

[1] China Med Univ, Dept Pharmacol, Sch Pharmaceut Sci, Shenyang 110001, Liaoning Provin, Peoples R China

[2] China Med Univ, Lab Anim Ctr, Shenyang 110001, Liaoning Provin, Peoples R China

[3] China Med Univ, Coll Basic Med Sci, Dept Biomed Engn, Shenyang 110001, Liaoning Provin, Peoples R China

来源：

MOLECULAR NEUROBIOLOGY | 2014年 / 49卷 / 03期

关键词：

EGCG; NGF; TrkA/p75(NTR) balance; APP/PS1 transgenic mouse; Learning and memory deficits; ALZHEIMERS-DISEASE; AMYLOID-BETA; GREEN TEA; MOUSE MODEL; COGNITIVE IMPAIRMENT; PASSIVE-AVOIDANCE; BASAL FOREBRAIN; WATER-MAZE; CELL-DEATH; RECEPTORS;

D O I：

10.1007/s12035-013-8608-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Alzheimer's disease (AD) is pathologically characterized by deposition of beta-amyloid (A beta) peptides, which closely correlates with the balance of nerve growth factor (NGF)-related TrkA/p75(NTR) signaling. (-)-Epigallocatechin-3- gallate (EGCG) is used for prevention and treatment of many neurodegenerative diseases, including AD. However, whether the neuroprotective effects of EGCG treatment were via modulating the balance of TrkA/p75(NTR) signaling was still unknown. In this study, we found that EGCG treatment (2 mg . kg(-1) . day(-1)) dramatically ameliorated the cognitive impairments, reduced the overexpressions of A beta(1-40) and amyloid precursor protein (APP), and inhibited the neuronal apoptosis in the APP/PS1 mice. Interestingly, the EGCG treatment enhanced the relative expression level of NGF by increasing the NGF/proNGF ratio in the APP/PS1 mice. Moreover, after EGCG treatment, TrkA signaling was activated by increasing the phosphorylation of TrkA following the increased phosphorylation of c-Raf, ERK1/2, and cAMP response element-binding protein (CREB), simultaneously the p75(NTR) signaling was significantly inhibited by decreasing the p75(ICD) expression, JNK2 phosphorylation, and cleaved-caspase 3 expression, so that the A beta deposits and neuronal apoptosis in the hippocampus were inhibited.

引用

页码：1350 / 1363

页数：14

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