β淀粉样蛋白病理降低了阿尔茨海默病小鼠模型中大脑 mGluR5 的密度。
Aβ pathology downregulates brain mGluR5 density in a mouse model of Alzheimer.
机构信息
Department of Nuclear Medicine, School of Medicine, Inha University, Incheon, South Korea.
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
出版信息
Neuropharmacology. 2018 May 1;133:512-517. doi: 10.1016/j.neuropharm.2018.02.003. Epub 2018 Feb 7.
The aim of the present study was to evaluate functional changes of mGluR5 expression in advanced Alzheimer's disease (AD) using positron emission tomography (PET) with an mGluR5 specific radiotracer ([F]FPEB) in 5xFAD AD model. Subsequently, in the same animal, mGluR5 expression was quantified by immunoassay techniques. The non-displaceable binding potential values for mGluR5 was estimated by the Logan's graphical analysis. Brain PET imaging revealed that radioactivities in the hippocampus and the striatum were significantly lower in 5xFAD mice compared to control animals. Binding values were also significantly lowered in 5xFAD mice. This decline was validated by immunoblotting of protein isolates from brain tissues, as the mean band density for 5xFAD mice had a lower mGluR5 intensity than for wild type mice. These results indicated that mGluR5 levels in 5xFAD mice were down regulated in the limbic system.
本研究旨在使用正电子发射断层扫描 (PET) 技术，利用 mGluR5 特异性放射性示踪剂 ([F]FPEB)，评估 5xFAD AD 模型中晚期阿尔茨海默病 (AD) 中 mGluR5 表达的功能变化。随后，在同一动物中，通过免疫测定技术定量 mGluR5 表达。通过 Logan 的图形分析估算 mGluR5 的不可置换结合势能值。脑 PET 成像显示，与对照动物相比，5xFAD 小鼠的海马体和纹状体中的放射性显著降低。5xFAD 小鼠的结合值也显著降低。脑组织蛋白分离物的免疫印迹验证了这一下降，因为与野生型小鼠相比，5xFAD 小鼠的平均条带密度的 mGluR5 强度较低。这些结果表明，5xFAD 小鼠的边缘系统中 mGluR5 水平下调。
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