Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis.
Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis.
复制标题
相关的异光谱脂肪组学用于多发性硬化症中remer髓的生物分子分析。
DOI：
10.1021/acscentsci.7b00367
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发表时间：
2018-01-24
影响因子：
18.2
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Bergholt MS;Serio A;McKenzie JS;Boyd A;Soares RF;Tillner J;Chiappini C;Wu V;Dannhorn A;Takats Z;Williams A;Stevens MM
分析大脑中的脂质成分和分布对于研究呈现局灶性脱髓鞘病变的白质病理很重要，例如多发性硬化症。一些病变可以内源性地重新形成髓鞘。治疗的目的是加强这一修复过程，以减少患者的神经退化和残疾进展。在这种情况下，提供精确的分子分类和明确的定位的脂肪组学分析对于检测髓鞘脂类含量的变化至关重要。在这里，我们发展了一种基于共注册拉曼光谱、解吸电喷雾电离质谱仪(DESI-MS)和免疫荧光成像的相关异谱脂体(HSL)方法。我们使用HSL来研究在诱导局灶性脱髓鞘小鼠模型和多发性硬化症患者的体外病变中脱髓鞘和重新髓鞘的结构和组成的脂类分布。拉曼光谱和DESI-MS成像的像素共配准产生了用于关联髓鞘的生物分子结构和组成的异谱图谱。多元回归分析首次使基于拉曼的复杂组织中高度特异的脂肪亚型的评估成为可能。这种方法揭示了重新髓鞘形成的时间动力学，并首次表明新形成的髓鞘具有与正常髓鞘不同的脂组成。HSL能够进行详细的分子髓鞘表征，可以大大改善目前对多发性硬化症重新髓鞘形成的了解，并为在动物模型中评估重新髓鞘形成治疗提供了一种策略。一种新的结合拉曼光谱和DESI质谱学的异谱分析技术可以揭示多发性硬化症重新髓鞘形成过程中的脂质成分差异。
Analyzing lipid composition and distribution within the brain is important to study white matter pathologies that present focal demyelination lesions, such as multiple sclerosis. Some lesions can endogenously re-form myelin sheaths. Therapies aim to enhance this repair process in order to reduce neurodegeneration and disability progression in patients. In this context, a lipidomic analysis providing both precise molecular classification and well-defined localization is crucial to detect changes in myelin lipid content. Here we develop a correlated heterospectral lipidomic (HSL) approach based on coregistered Raman spectroscopy, desorption electrospray ionization mass spectrometry (DESI-MS), and immunofluorescence imaging. We employ HSL to study the structural and compositional lipid profile of demyelination and remyelination in an induced focal demyelination mouse model and in multiple sclerosis lesions from patients ex vivo. Pixelwise coregistration of Raman spectroscopy and DESI-MS imaging generated a heterospectral map used to interrelate biomolecular structure and composition of myelin. Multivariate regression analysis enabled Raman-based assessment of highly specific lipid subtypes in complex tissue for the first time. This method revealed the temporal dynamics of remyelination and provided the first indication that newly formed myelin has a different lipid composition compared to normal myelin. HSL enables detailed molecular myelin characterization that can substantially improve upon the current understanding of remyelination in multiple sclerosis and provides a strategy to assess remyelination treatments in animal models. A novel heterospectral analysis technique combining Raman spectroscopy and DESI mass spectrometry allows uncovering of lipid compositional differences during remyelination in multiple sclerosis.
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影响因子：
18.2
作者：
Bergholt, Mads S.;St-Pierre, Jean-Philippe;Offeddu, Giovanni S.;Parmar, Paresh A.;Albro, Michael B.;Puetzer, Jennifer L.;Oyen, Michelle L.;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
影响因子：
30.8
作者：
Lappe-Siefke, C;Goebbels, S;Nave, KA
通讯作者：
Nave, KA
DOI：
10.1016/j.saa.2004.11.017
发表时间：
2005-05-01
影响因子：
4.4
作者：
Krafft, C;Neudert, L;Salzer, R
通讯作者：
Salzer, R
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin
影响因子：
5
作者：
Patani, R.;Balaratnam, M.;Reynolds, R.
通讯作者：
Reynolds, R.