Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2.
Neuroimage. 2012 Mar;60(1):376-83. doi: 10.1016/j.neuroimage.2011.11.069. Epub 2011 Dec 16.
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.
神经退行性病变的关键问题，包括阿尔茨海默病和其他神经退行性疾病，与为什么某些神经元能够存活的问题密切相关。答案需要对单细胞中的生化变化有详细的了解。傅里叶变换红外显微镜是一种用于原位生物分子成像的极好工具，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）能够对神经元进行无标记的亚细胞成像和生化分析，其像素间距比当前系统增加了两个数量级。IRENI 的功能使得现在可以原位研究单个神经元的变化，并使用未染色、未固定组织中的天然存在成分的生化特征来表征其周围环境。我们展示了来自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，这些模型表现出不同的发病特征。对核光谱特征进行数据处理可揭示 TgCRND8 小鼠中单个海马神经元和位于淀粉样斑块附近的神经元。在淀粉样斑块的核心周围，甚至首次在核心内部检测到升高的脂质，这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允许对神经元层进行特征描述。IRENI 图像还以前所未有的清晰度和明显的光谱变化揭示了空间分辨数据，包括来自包括光感受器、神经元细胞体和突触在内的亚区的老鼠视网膜切片。视网膜层的生化组成可用于研究与疾病过程和饮食改变相关的变化。
