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Combination of ESI and MALDI mass spectrometry for qualitative semi-quantitative and in situ analysis of gangliosides in brain

机译:ESI和MALDI质谱联用对脑中神经节苷脂进行定性半定量和原位分析

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摘要

Gangliosides are a family of complex lipids that are abundant in the brain. There is no doubt the investigations about the distribution of gangliosides in brian and the relationship between gangliosides and Alzheimer’s disease is profound. However, these investigations are full of challenges due to the structural complexity of gangliosides. In this work, the method for efficient extraction and enrichment of gangliosides from brain was established. Moreover, the distribution of gangliosides in brain was obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). It was found that 3-aminoquinoline (3-AQ) as matrix was well-suited for MALDI MS analysis of gangliosides in negative ion mode. In addition, the pretreatment by ethanol (EtOH) cleaning brain section and the addition of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI analysis was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was respectively acquired by electrospray ionization (ESI) MS and MALDI MSI, and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technology, the distribution of gangliosides in amyloid precursor protein transgenic mouse brain was obtained, which may provide a new insight for bioresearch of Alzheimer’s disease (AD).
机译:神经节苷脂是大脑中丰富的复杂脂质家族。毫无疑问,有关神经节苷脂在布赖恩病中分布的研究以及神经节苷脂与阿尔茨海默氏病之间的关系是深远的。然而,由于神经节苷脂的结构复杂性,这些研究充满了挑战。在这项工作中,建立了一种从大脑中有效提取和富集神经节苷脂的方法。此外,神经节苷脂在大脑中的分布是通过基质辅助激光解吸电离(MALDI)质谱成像(MSI)获得的。发现以3-氨基喹啉(3-AQ)为基质非常适合在阴离子模式下对神经节苷脂进行MALDI MS分析。此外,当使用MALDI MSI分析时,通过乙醇(EtOH)清洁脑部的预处理和添加甲酸铵可大大改善脑部神经节苷脂的MS信号。通过电喷雾电离(ESI)MS和MALDI MSI分别获得了大脑皮层,海马和小脑中神经节苷脂的分布,并比较了这些数据,以评估MALDI MSI的可靠性。此外,应用MALDI MSI技术,获得了神经节苷脂在淀粉样前体蛋白转基因小鼠脑中的分布,这可能为阿尔茨海默氏病(AD)的生物研究提供新的见解。

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