Berberine attenuates cognitive deficits via improving NGF signaling in AD mice
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摘要: 目的观察小檗碱对阿尔茨海默病(AD)模型小鼠脑内神经生长因子(NGF)通路变化及改善AD小鼠学习记忆机制。方法以APP/PS1双转基因小鼠为模型, 采用Y迷宫进行学习记忆能力评价, Western blot检测NGF及相关通路蛋白表达。结果与对照组[(77.57±11.81)%]比较, 模型组小鼠自发交替反应率[(55.71±12.33)%]降低(P<0.01);与模型组比较, 小檗碱组小鼠自发交替反应率[(70.93±15.99)%]升高(P<0.01);与对照组比较, 模型组小鼠海马NGF、络氨酸激酶(TrkA)、磷酸化蛋白激酶(ERK)、磷酸化环磷腺苷效应元件结合蛋白(CREB)表达水平[分别为(0.186±0.031)、(0.187±0.019)、(0.572±0.101)、(0.499±0.138)]均降低(均P<0.05);与模型组比较, 小檗碱组小鼠海马NGF、TrkA、磷酸化ERK、磷酸化CREB表达水平[分别为(0.592±0.043)、(0.281±0.085)、(0.906±0.097)、(0.895±0.152)]均升高(均P<0.05)。结论小檗碱可以改善APP/PS1小鼠学习记忆障碍, 其机制可能与调控NGF通路有关。
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关键词:
- 小檗碱 /
- 阿尔茨海默病(AD) /
- 认知障碍 /
- 神经生长因子(NGF)
Abstract: ObjectiveTo investigate the change of nerve growth factor(NGF) signaling and mechanisms of berberine on learning and memory deficits in Alzheimer's disease(AD) mice.MethodsWe adopted APP/PS1 mice as AD animal model; we used Y maze to measure learning and memory function and Western blot to investigate the protein expression levels.ResultsCompared with the control mice(77.57±11.81),the APP/PS1 mice exhibited reduced spontaneous alternation behavior(55.71±12.33)(P<0.01).Berberine(30 mg/kg) attenuate the impairment of spontaneous alternation behavior(70.93±15.99)(P<0.01).The expression levels of NGF,tyrosine kinases(TrkA),phosphorylated extracellular regulated protein kinases(p-ERK),and phosphorylated cAMP-response element binding protein(p-CREB) in the hippocampus were lower in APP/PS1 mice compared to those of the control mice(P<0.05),but were higher in the berberine(30 mg/kg) treated mice compared to those of the APP/PS1 mice(P<0.05).ConclusionBerberine attenuates learning and memory impairments in APP/PS1 mice,possibly through the NGF signaling pathway. -
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