Soy-Based Diet Exacerbates Seizures in Mouse Models of Neurological Disease
Soy-Based Diet Exacerbates Seizures in Mouse Models of Neurological Disease
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DOI：
10.3233/jad-2012-121426
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Malter, James S.
中科院分区：
文献类型：
--
作者：
Westmark, Cara J.;Westmark, Pamela R.;Malter, James S.
癫痫是许多神经疾病的常见表型，包括阿尔茨海默病、唐氏综合症和脆性X综合征。这些疾病的小鼠模型过度表达淀粉样β蛋白前体(AβPP)和淀粉样β蛋白(Aβ)，并且对听源性癫痫(AGS)高度敏感。我们观察到以酪蛋白为基础的纯净饮食(D07030301)与标准的含大豆蛋白的非纯净饮食(Purina 5015)相比，这些小鼠的AGS降低。我们在这篇手稿中的目标是确定Purina 5015中的大豆蛋白，特别是大豆异黄酮是否与癫痫表型有关。对饲喂普瑞纳5015、D07030301、含大豆蛋白的D07030301或D07030301添加大豆异黄酮(750 mg/kg大豆苷元或染料木素)的幼鼠进行了野跑、AGS和死亡率的评估。短期(3天)用Purina 5015诱导阿尔茨海默病小鼠的狂跑和AGS。用添加大豆苷元的饮食治疗3天，而不是金雀异黄素，在野生型小鼠中引起狂野奔跑。为了了解大豆苷元活性的机制，我们评估了用大豆苷元或染料木素处理的原代、培养的野生型神经元中树突状AβPP的表达。在体外，大豆苷元显著增加树突状AβPP。因此，大豆异黄酮型大豆苷元可在体内诱导癫痫发作，并在体外改变AβPP的表达。这些结果对以大豆为基础的饮食的个体以及啮齿动物模型研究具有重要的意义。
Seizures are a common phenotype in many neurological disorders including Alzheimer's disease, Down syndrome, and fragile X syndrome. Mouse models of these disorders overexpress amyloid-beta protein precursor (A beta PP) and amyloid-beta (A beta) and are highly susceptible to audiogenic-induced seizures (AGS). We observed decreased AGS in these mice fed a casein-based, purified diet (D07030301) as opposed to a standard soy protein-containing, non-purified diet (Purina 5015). Our objective in this manuscript was to determine if soy protein, and in particular soy isoflavones, in the Purina 5015 were contributing to the seizure phenotype. Wild running, AGS, and death rates were assessed in juvenile mice fed Purina 5015, D07030301, D07030301 containing soy protein, or D07030301 supplemented with individual isoflavones (750 mg/kg daidzein or genistein). A short treatment (3 days) with Purina 5015 induced wild running and AGS in Alzheimer's disease mice. A 3-day treatment with daidzein-supplemented diet, but not genistein, induced wild running in wild type mice. To understand the mechanism underlying daidzein activity, we assessed dendritic A beta PP expression in primary, cultured, wild type neurons treated with daidzein or genistein. In vitro, daidzein significantly increased dendritic A beta PP. Thus, the soy isoflavone daidzein recapitulated seizure induction in vivo and altered A beta PP expression in vitro. These results have important implications for individuals on soy-based diets as well as for rodent model research.