Ginsenoside Rg1 Attenuates Amyloid-β Content, Regulates PKA/CREB Activity, and Improves Cognitive Performance in SAMP8 Mice

被引:107
作者
Shi, Yan-Qing [2 ]
Huang, Tian-Wen [1 ,2 ]
Chen, Li-Min [2 ]
Pan, Xiao-Dong [1 ,2 ]
Zhang, Jing [2 ]
Zhu, Yuan-Gui [1 ,2 ,3 ]
Chen, Xiao-Chun [1 ,2 ,3 ]
机构
[1] Fujian Med Univ, Affiliated Union Hosp, Dept Neurol, Fuzhou 350001, Fujian, Peoples R China
[2] Fujian Inst Geriatr, Fuzhou, Fujian, Peoples R China
[3] Fujian Med Univ, Ctr Neurobiol, Fuzhou 350001, Fujian, Peoples R China
关键词
Alzheimer's disease; amyloid-beta; CREB; ginsenoside Rg1; PKA; senescence-accelerated mouse prone8; SENESCENCE-ACCELERATED MOUSE; LONG-TERM POTENTIATION; ELEMENT-BINDING PROTEIN; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; CYCLIC-AMP; GENE-EXPRESSION; LATE-PHASE; TRANSCRIPTIONAL REGULATION; MEMORY CONSOLIDATION;
D O I
10.3233/JAD-2010-1296
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
It is well established that the presence of soluble amyloid-beta protein (A beta) correlates with the severity of dementia in Alzheimer's disease (AD). Several lines of evidence indicate that cyclic AMP responsive element binding protein (CREB) and protein kinase A (PKA) are involved in soluble A beta-trigged disruption of synaptic plasticity in early AD. Previously we demonstrated the beneficial effects of ginsenoside Rg1 on A beta-induced neuronal insult. Therefore, in the present study, we examined the effects of long-term consumption of Rg1 on the cerebral A beta content and PKA/CREB signaling molecules, as well as cognitive performance in senescence-accelerated mouse prone 8 (SAMP8). Notably, a significant dose-dependent reduction of soluble A beta 1-40 was shown in the hippocampus of SAMP8 mice after administration with ginsenoside Rg1 for 3 months. Furthermore, Rg1 treatment resulted in a significant decrease of hippocampal PKA RII alpha level (isoform II alpha of the regulatory subunit of PKA). In contrast, phospho-CREB and brain derived neurotrophic factor (BDNF) levels were dramatically increased in the hippocampus of SAMP8 treated with Rg1. Additionally, administration of ginsenoside Rg1 consequently improved learning and memory outcomes in SAMP8 mice. These data suggest that long-term consumption of ginsenoside Rg1 may delay cognitive decline, associated with significant effects on A beta generation, PKA/CREB activity, as well as BDNF content in the brain. These data provide further support for the therapeutic or intervention potency of ginsenoside Rg1 in the early stage of AD.
引用
收藏
页码:977 / 989
页数:13
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