Imaging MALDI mass spectrometry using an oscillating capillary nebulizer matrix coating system and its application to analysis of lipids in brain from a mouse model of Tay-Sachs/Sandhoff disease
Imaging MALDI mass spectrometry using an oscillating capillary nebulizer matrix coating system and its application to analysis of lipids in brain from a mouse model of Tay-Sachs/Sandhoff disease
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DOI：
10.1021/ac702350g
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发表时间：
2008-04-15
影响因子：
7.4
通讯作者：
Sullards, M. Cameron
中科院分区：
文献类型：
--
作者：
Chen, Yanfeng;Allegood, Jeremy;Sullards, M. Cameron
通过基质辅助激光解吸/电离质谱法（MALDI-MS）进行的组织成像的质量取决于基质沉积的有效性，特别是对于可能溶解在用于基质应用的溶剂中的脂质。本文介绍了使用振荡毛细管雾化器（OCN）喷雾小液滴的基质气溶胶到样品表面上，以改善基质的均匀性，降低晶体尺寸，并控制溶剂的影响。然后将该系统应用于hexb基因纯合破坏小鼠脑组织切片的分析（hexb（-/-）），一种Tay-Sachs和Sandhoff病模型，与功能正常的杂合子这允许分析和定位许多不同的脂质种类，并且特别感兴趣的是神经节苷脂GM 2、无唾液酸-GM 2（GA 2）、和硫苷脂（ST）。这些化合物的存在通过使用电喷雾电离结合串联质谱法（MS/MS）分析脑提取物来确认。GM 2和GA 2的神经酰胺骨架的主要脂肪酸通过组织成像MS和ESI-MS/MS两者鉴定为硬脂酸（18：0）与ST的神经酸（24：1）。GM 2和GA 2在hexb（-/-）中高度升高，并且都定位于小脑的颗粒细胞区域。然而，ST主要位于小脑的有髓纤维（白色物质）区域以及脑干中，分布相对均匀，并且hexb（+/-）和hexb（-/-）脑的相对信号强度相似。还观察到许多其他脂质亚类存在不同的定位;因此，成像MALDI-MS可用于“脂质组学”研究。这些结果说明了组织成像MALDI-MS与OCN基质沉积的有用性，用于组织中脂质的组织学比较，例如来自Tay-Sachs和Sandhoff病小鼠模型的脑。
The quality of tissue imaging by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) depends on the effectiveness of the matrix deposition, especially for lipids that may dissolve in the solvent used for the matrix application. This article describes the use of an oscillating capillary nebulizer (OCN) to spray small droplets of matrix aerosol onto the sample surface for improved matrix homogeneity, reduced crystal size, and controlled solvent effects. This system was then applied to the analysis of histological slices of brains from mice with homozygous disruption of the hexb gene (hexb(-/-)), a model of Tay-Sachs and Sandhoff disease, versus the functionally normal heterozygote (hexb(+/-)) by imaging MALDI-MS. This allowed profiling and localization of many different lipid species, and of particular interest, ganglioside GM2, asialo-GM2 (GA2), and sulfatides (ST). The presence of these compounds was confirmed by analysis of brain extracts using electrospray ionization in conjunction with tandem mass spectrometry (MS/MS). The major fatty acid of the ceramide backbone of both GM2 and GA2 was identified as stearic acid (18:0) versus nervonic acid (24: 1) for ST by both tissue-imaging MS and ESI-MS/MS. GM2 and GA2 were highly elevated in hexb(-/-) and were both localized in the granular cell region of the cerebellum. ST, however, was localized mainly in myelinated fiber (white matter) region of the cerebellum as well as in the brain stem with a relatively uniform distribution and had similar relative signal intensity for both hexb(+/-) and hexb(-/-) brain. It was also observed that there were distinct localizations for numerous other lipid subclasses; hence, imaging MALDI-MS could be used for "lipidomic" studies. These results illustrate the usefulness of tissue-imaging MALDI-MS with matrix deposition by OCN for histologic comparison of lipids in tissues such as brains from this mouse model of Tay-Sachs and Sandhoff disease.