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Article type: Research Article
Authors: Shi, Yan-Qinga | Huang, Tian-Wena; b | Chen, Li-Mina | Pan, Xiao-Donga; b | Zhang, Jinga | Zhu, Yuan-Guia; b; c | Chen, Xiao-Chuna; b; c; *
Affiliations: [a] Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China | [b] Department of Neurology, the Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China | [c] The Centre of Neurobiology of Fujian Medical University; Fuzhou, Fujian, People's Republic of China
Correspondence: [*] Correspondence to: Xiao-Chun Chen, M.D., Ph.D., Department of Neurology, The Affiliated Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, People's Republic of China. Tel.: +86 591 8333 3995; Fax: +86 591 8337 0393; E-mail: [email protected].
Abstract: It is well established that the presence of soluble amyloid-β protein (Aβ) 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 Aβ-trigged disruption of synaptic plasticity in early AD. Previously we demonstrated the beneficial effects of ginsenoside Rg1 on Aβ-induced neuronal insult. Therefore, in the present study, we examined the effects of long-term consumption of Rg1 on the cerebral Aβ 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 Aβ1-40 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 RIIα level (isoform IIα 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 Aβ 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.
Keywords: Alzheimer's disease, amyloid-β, CREB, ginsenoside Rg1, PKA, senescence-accelerated mouse prone8
DOI: 10.3233/JAD-2010-1296
Journal: Journal of Alzheimer's Disease, vol. 19, no. 3, pp. 977-989, 2010
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