Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer's Disease.
Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer's Disease.
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DOI：
10.3390/ijms14035576
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发表时间：
2013-03-11
影响因子：
5.6
通讯作者：
Zhang LF
中科院分区：
文献类型：
--
作者：
Wang DM;Yang YJ;Zhang L;Zhang X;Guan FF;Zhang LF
在人和小鼠模型中，淀粉样蛋白-β (Aβ)诱导的海马突触可塑性损伤是阿尔茨海默病（AD）早期记忆丧失的潜在机制。抑制钙/钙调素依赖性蛋白激酶II （CaMKII）自磷酸化在长期记忆中起重要作用。本研究从柚子皮中分离柚皮苷，并在APPswe/PS1dE9转基因AD小鼠模型中研究其对长期记忆的影响。将3月龄的APPswe/PS1dE9转基因小鼠随机分为载药组、柚皮苷（50或100 mg/kg体重/d）组和阿立赛普（2 mg/kg体重/d）组。16周后，我们观察到柚皮苷（100 mg/kg体重/天）增强了CaMKII的自磷酸化，增加了CaMKII依赖位点α-氨基-3-羟基-5-甲基-4-异唑丙酸（AMPA）受体的磷酸化，提高了长期学习和记忆能力。这些发现表明，CaMKII活性的增加可能是柚皮素改善APPswe/PS1dE9转基因AD小鼠模型长期认知功能的机制之一。
The Amyloid-β (Aβ)-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer’s disease (AD) in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species) and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day) groups, or an Aricept (2 mg/kg body weight/day) group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day) enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.
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影响因子：
34.7
作者：
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通讯作者：
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影响因子：
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作者：
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Bydlowski, Sergio Paulo
影响因子：
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作者：
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