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在转基因小鼠模型中使用与抗体aβ1-40偶联的中空氧化锰纳米颗粒对淀粉样斑块进行磁共振成像。

Magnetic resonance imaging of amyloid plaques using hollow manganese oxide nanoparticles conjugated with antibody aβ1-40 in a transgenic mouse model.

作者信息

Kim Jae-Hun, Ha Tae Lin, Im Geun Ho, Yang Jehoon, Seo Sang Won, Lee In Su, Lee Jung Hee

机构信息

Departments of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Neuroreport. 2013 Jan 9;24(1):16-21. doi: 10.1097/WNR.0b013e32835ba850.

Abstract

In this study, we have shown the feasibility of hollow manganese oxide nanoparticles (HMON) conjugated with an antibody of Aβ1-40 peptide (abAβ40) (HMON-abAβ40) for MRI of amyloid plaques in APP/PS1 transgenic mice. MR brain images in APP/PS1 transgenic mice and their nontransgenic littermates were acquired using a 7.0 T MRI system before, and 24 and 72 h after an injection of HMON-abAβ40. After the injection of HMON-abAβ40, we found hyperenhanced spots in the frontal cortex area on T1-weighted MR images for transgenic mice, which corresponded qualitatively to amyloid plaques detected by thioflavin-S staining. For quantitative analysis, percent MR signal changes in six brain regions (olfactory cortex, frontal cortex, cerebral cortex, thalamus, hippocampus, and cerebellar cortex) were compared between transgenic and wild-type mice. We found significant increases in the percent MR signal changes in the olfactory cortex, frontal cortex, cerebral cortex, and hippocampus, but there were no significant differences in the thalamus and cerebellar cortex for transgenic mice compared with wild-type mice. This unique strategy allowed us to detect brain regions subjected to amyloid plaque deposition in Alzheimer's disease transgenic mouse models and has a potential to be developed for human applications, which has a current utility in preclinical research, particularly in monitoring therapeutic response for drug development in Alzheimer's disease.

摘要

在本研究中,我们已证明与Aβ1-40肽抗体(abAβ40)偶联的中空氧化锰纳米颗粒(HMON)(HMON-abAβ40)用于APP/PS1转基因小鼠淀粉样斑块磁共振成像(MRI)的可行性。在注射HMON-abAβ40之前、之后24小时和72小时,使用7.0 T MRI系统采集APP/PS1转基因小鼠及其非转基因同窝小鼠的脑部MR图像。注射HMON-abAβ40后,我们在转基因小鼠的T1加权MR图像上发现额叶皮质区域有强化增强斑点,这在质量上与硫黄素-S染色检测到的淀粉样斑块相对应。为了进行定量分析,比较了转基因小鼠和野生型小鼠六个脑区(嗅皮质、额叶皮质、大脑皮质、丘脑、海马体和小脑皮质)的MR信号变化百分比。我们发现转基因小鼠的嗅皮质、额叶皮质、大脑皮质和海马体的MR信号变化百分比显著增加,但与野生型小鼠相比,转基因小鼠的丘脑和小脑皮质没有显著差异。这种独特的策略使我们能够在阿尔茨海默病转基因小鼠模型中检测到发生淀粉样斑块沉积的脑区,并且有潜力开发用于人类应用,目前在临床前研究中具有实用性,特别是在监测阿尔茨海默病药物开发的治疗反应方面。

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