Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer's disease mouse models.
Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer's disease mouse models.
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DOI：
10.1016/j.neuropharm.2010.03.011
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发表时间：
2010-09
影响因子：
4.7
通讯作者：
Jenkins, Bruce G.
中科院分区：
文献类型：
--
作者：
Choi, Ji-Kyung;Carreras, Isabel;Dedeoglu, Alpaslan;Jenkins, Bruce G.
有证据表明，在阿尔茨海默病小鼠模型中，肌醇异构体可能有助于防止Aβ片段毒性原纤维的形成。scylo -肌醇是最有希望治疗阿尔茨海默病（AD）的肌醇异构体之一，可以在人类受试者中使用MRS检测到。在这篇论文中，我们在两种不同的AD小鼠模型（APP×PS1和APP×PS1×tau）中证明，我们可以检测到在喂食了16.5mg/L的水（相当于约3.3mg/kg/天）的小鼠的海马体和额叶皮质中增加的scylo -肌醇。我们使用溶液MRS和高分辨率魔角旋转（HRMAS）来检测完整脑组织，以确保检测到任何与膜相关的scylo -肌醇。通过脑提取物，我们检测到，与正常饮食相比，喂食scyllo-肌醇的AD小鼠的scyllo-肌醇增加了3.0倍（p<0.001）。HRMAS检测到肌醇含量增加2.2-2.4倍（p<0.001）。scyllo -肌醇治疗与海马中谷氨酰胺的增加有关。海马区肌醇浓度高于额叶皮质区。小鼠的肌醇浓度低于人类（约100μM vs 500μM）。考虑到高信噪比的人体磁共振数据可以很容易地测量到三基肌醇，这些数据表明磁共振将被证明对评估AD受试者的肌醇治疗试验有用。
There is evidence that inositol isomers may help protect against formation of toxic fibrils of Aβ fragments in Alzheimer disease mouse models. Scyllo-inositol is one of the more promising inositol isomers for the potential treatment of Alzheimer's disease (AD) and can be detected using MRS in human subjects. In this manuscript we demonstrate using MRS, in two different mouse models of AD (APP×PS1 and APP×PS1×tau), that we could detect increased scyllo-inositol in the hippocampus and frontal cortex in mice fed water supplemented with 16.5mg/L of scyllo-inositol equivalent to about 3.3mg/kg/day. We used both brain extracts using solution MRS as well as intact brain tissue using high resolution magic angle spinning (HRMAS) to ensure that any membrane associated scyllo-inositol would be detected. By brain extracts we detected a 3.0 fold increase in scyllo-inositol in the scyllo-fed AD mice compared to normal diet (p<0.001). Using HRMAS we detected a 2.2-2.4-fold increase in scyllo-inositol (p<0.001). Scyllo-inositol treatment was associated with an increase in glutamine in hippocampus. The concentrations of scyllo-inositol were higher in the hippocampus than in the frontal cortex. Mice have a smaller concentration of scyllo-inositol than humans (ca. 100μM vs. 500μM in humans). Given the ease with which scyllo-inositol can be measured in human MRS data with high signal to noise ratios, these data suggest that MRS will prove useful for evaluation of inositol treatment trials in AD subjects.
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影响因子：
2.9
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