Biochemical label-free tissue imaging with subcellular-resolution synchrotron FTIR with focal plane array detector
Biochemical label-free tissue imaging with subcellular-resolution synchrotron FTIR with focal plane array detector
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DOI：
10.1016/j.neuroimage.2011.11.069
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发表时间：
2012-03-01
期刊：
影响因子：
5.7
通讯作者：
Gough, K. M.
中科院分区：
文献类型：
--
作者：
Kastyak-Ibrahim, M. Z.;Nasse, M. J.;Gough, K. M.
在阿尔茨海默病和其他神经退行性疾病中，神经退化的原因的关键问题与为什么某些神经元存活的问题密切相关。答案需要对单个细胞的生化变化有详细的了解。傅里叶变换红外微光谱学是生物分子原位成像的一种优秀工具，但分辨率有限。威斯康星大学麦迪逊分校同步辐射中心的中红外光束线IRENI（红外环境成像）使神经元的无标签亚细胞成像和生化分析比当前系统的像素间距增加了两个数量级。有了IRENI的能力，现在可以研究单个神经元的原位变化，并仅使用未染色、未固定组织中自然产生的成分的生化特征来表征其周围环境。我们介绍了两种阿尔茨海默病转基因小鼠模型（TgCRND8和3xTg）的大脑分析示例，它们表现出不同的发病机制特征。对核谱特征的数据处理揭示了TgCRND8小鼠海马神经元和淀粉样蛋白斑块附近的神经元。升高的脂质在淀粉样斑块周围被检测到，这是第一次在淀粉样斑块的致密核心内被检测到，为炎症和聚集作用提供了支持。视网膜中饱和和不饱和脂肪酸酯含量的分析可以表征神经元层。IRENI图像还显示了空间分辨率数据，具有前所未有的清晰度和明显的光谱变化，来自小鼠视网膜切片的子区域，包括光感受器、神经元细胞体和突触。视网膜各层的生化组成可用于研究与疾病进程和饮食改变相关的变化。(C) 2011爱思唯尔公司版权所有。
The critical questions into the cause of neural degeneration, in Alzheimer disease and other neurodegenerative disorders, are closely related to the question of why certain neurons survive. Answers require detailed understanding of biochemical changes in single cells. Fourier transform infrared microspectroscopy is an excellent tool for biomolecular imaging in situ, but resolution is limited. The mid-infrared beamline IRENI (InfraRed ENvironmental Imaging) at the Synchrotron Radiation Center, University of Wisconsin-Madison, enables label-free subcellular imaging and biochemical analysis of neurons with an increase of two orders of magnitude in pixel spacing over current systems. With IRENI's capabilities, it is now possible to study changes in individual neurons in situ, and to characterize their surroundings, using only the biochemical signatures of naturally-occurring components in unstained, unfixed tissue. We present examples of analyses of brain from two transgenic mouse models of Alzheimer disease (TgCRND8 and 3xTg) that exhibit different features of pathogenesis. Data processing on spectral features for nuclei reveals individual hippocampal neurons, and neurons located in the proximity of amyloid plaque in TgCRND8 mouse. Elevated lipids are detected surrounding and, for the first time, within the dense core of amyloid plaques, offering support for inflammatory and aggregation roles. Analysis of saturated and unsaturated fatty acid ester content in retina allows characterization of neuronal layers. IRENI images also reveal spatially-resolved data with unprecedented clarity and distinct spectral variation, from sub-regions including photoreceptors, neuronal cell bodies and synapses in sections of mouse retina. Biochemical composition of retinal layers can be used to study changes related to disease processes and dietary modification. (C) 2011 Elsevier Inc. All rights reserved.