甲基苯丙胺暴露对神经病理性蛋白APP及p-tau表达的影响
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国家自然科学基金(81202230,81673213);江苏省自然科学基金(BK20151557); 江苏省科技厅重点病种规范化诊疗研究(BL2014088)


The effects of methamphetamine on the expression of pathological protein APP and p-tau
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    摘要:

    目的:观察甲基苯丙胺(methamphetamine,Meth)暴露后神经病理性蛋白β-淀粉样前体蛋白(amyloid precursor protein, APP)及p-tau表达的改变。方法:将30只C57BL/6J雄性小鼠随机分为对照组、生理盐水组,Meth组,Meth组腹腔注射给予10 mg/kg的剂量,1 d 2次,连续7 d。利用高尔基银染法观察Meth作用后大脑神经元数量及棘突的改变;采用Western blot法检测Meth暴露后神经病理性蛋白APP,p-tau表达的改变。结果:高尔基银染结果显示,Meth组与生理盐水组及对照组比较,神经元数量及棘突显著减少。通过Western blot发现Meth能剂量依赖及时间依赖性上调病理性蛋白β-APP及p-tau的表达,具有显著性差异(P<0.05)。此外,通过预孵L型钙通道的抑制剂硝苯地平,发现Meth引起的APP及p-tau上调显著被抑制。结论:Meth暴露可引起阿尔兹海默样病变,因而该研究可为Meth引起认知能力下降提供部分解释。

    Abstract:

    Objective: To investigate the effects of methamphetamine (Meth) on the protein expression of β-amyloid precursor protein(APP) and p-tau. Methods: Thirty C57BL/6J male mice were randomly divided into control group, saline treatment group and Meth treated group, then the mice were administrated intraperitoneally with 10 mg/kg Meth for 7 days and two times a day. The silver staining of Golgi apparatus was performed to investigate the number of neurons and the dendritic spines, and the pathological protein APP and p-tau were detected by western blot. Results: With the silver staining of Golgi apparatus, it showed that Meth significantly decreased the number of the neurons as well as the dendritic spines. With the Western blot assay, it suggested that Meth obviously up-regulated the pathological protein APP and p-tau expression in a dose- and time-dependent manner(P<0.05). Intriguingly, pre-incubated with the neural cells with nifedipine, a blocker of the L-type Ca2+ channel, substantially attenuated Meth-mediated up-regulation of APP and p-tau. Conclusion: Meth exposure contributes Alzheimer's disease-like pathological changes, therefore, the present work will provide some supports for Meth-induced cognitive decline.

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程 洁,蒋 雷,钱文溢,肖 杭,王 军,陈旭锋.甲基苯丙胺暴露对神经病理性蛋白APP及p-tau表达的影响[J].南京医科大学学报(自然科学版),2017,(12):1548-1552

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  • 收稿日期:2017-06-03
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  • 在线发布日期: 2017-12-25
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