Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice.
Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice.
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DOI：
10.1016/j.neuropharm.2009.11.002
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发表时间：
2010-05
影响因子：
4.7
通讯作者：
Luo, Yuan
中科院分区：
文献类型：
--
作者：
Hou, Yan;Aboukhatwa, Marwa A.;Lei, De-Liang;Manaye, Kebreten;Khan, Ikhlas;Luo, Yuan
越来越多的证据表明，抑郁症可能是阿尔茨海默病（AD）等神经系统疾病的原因和结果，抗抑郁药可能为目前的AD治疗提供一种替代策略。与传统抗抑郁药和圣约翰草的副作用和草药相互作用的关联，保证了研究新的抗抑郁药。银杏叶提取物（EGb 761）的抗抑郁作用已在抑郁症动物模型和人类志愿者中得到证实。我们在此报道，银杏黄酮醇、槲皮素和山母酚刺激脑源性神经营养因子BDNF/环AMP反应元件结合蛋白CREB/突触后密度蛋白PSD95磷酸化的抑郁相关信号通路，并降低双转基因AD小鼠（TgAPPswe/PS1e9）分离的神经元中淀粉样蛋白-β肽（Aβ）。此外，双转基因小鼠海马中BDNF表达增强，Aβ低聚物减少，这与小鼠的认知改善行为有关。目前的研究结果表明，天然黄酮醇刺激BDNF和降低a β毒性对阿尔茨海默病的治疗具有治疗意义。
Increasing evidence suggests that depression may be both a cause and consequence of neurological disorders such as Alzheimer’s disease (AD), and that antidepressants could provide an alternative strategy to current AD therapies. Association of side effect and herbal-drug interaction with conventional antidepressant and St. John’s wort warrant investigating new antidepressant drugs. Antidepressant effects of ginkgo biloba extract (EGb 761) have been demonstrated in animal models of depression and in human volunteers. We report here that ginkgo flavonols quercetin and kaempferol stimulates depression-related signaling pathways involving brain-derived neurotrophic factor BDNF/phosphorylation of cyclic AMP response element binding protein CREB/postsynaptic density proteins PSD95, and reduces amyloid-β peptide (Aβ) in neurons isolated from double transgenic AD mouse (TgAPPswe/PS1e9). In addition, enhanced BDNF expression and reduction of Aβ oligomers was confirmed in hippocampus of the double transgenic mice administered with flavonol, which correlates with cognitive improvement behaviors in these mice. The present results suggest that stimulating BDNF and reducing Aβ toxicity by natural flavonols provide a therapeutic implication for treatment of AD.
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影响因子：
5.3
作者：
Lee, J;Fukumoto, H;Ingelsson, M
通讯作者：
Ingelsson, M
影响因子：
5.3
作者：
Nelson, Rhonda L.;Guo, Zhihong;Mattson, Mark P.
通讯作者：
Mattson, Mark P.
影响因子：
2.5
作者：
Matsuzaki, Kentaro;Yamakuni, Tohru;Ohizumi, Asushi
通讯作者：
Ohizumi, Asushi
影响因子：
3.6
作者：
Messaoudi, Michael;Bisson, Jean-Francois;Javelot, Herve
通讯作者：
Javelot, Herve
影响因子：
--
作者：
Cohen-Salmon, C;Venault, P;Chapouthier, G
通讯作者：
Chapouthier, G