Department of Neurology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Mail Slot 500, Little Rock, AR, 72205, USA.
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.
Neurochem Res. 2020 Nov;45(11):2586-2606. doi: 10.1007/s11064-020-03124-w. Epub 2020 Sep 19.
Metabolomic technologies including imaging mass spectrometry (IMS; also called mass spectrometry imaging, MSI, or matrix-assisted laser desorption/ionization-mass spectrometry imaging, MALDI MSI) are important methods to evaluate levels of many compounds in brain with high spatial resolution, characterize metabolic phenotypes of brain disorders, and identify disease biomarkers. ATP is central to brain energetics, and reports of its heterogeneous distribution in brain and regional differences in ATP/ADP ratios reported in IMS studies conflict with earlier studies. These discordant data were, therefore, analyzed and compared with biochemical literature that used rigorous methods to preserve labile metabolites. Unequal, very low regional ATP levels and low ATP/ADP ratios are explained by rapid metabolism during postmortem ischemia. A critical aspect of any analysis of brain components is their stability during and after tissue harvest so measured concentrations closely approximate their physiological levels in vivo. Unfortunately, the requirement for inactivation of brain enzymes by freezing or heating is not widely recognized outside the neurochemistry discipline, and procedures that do not prevent postmortem autolysis, including decapitation, brain removal/dissection, and 'snap freezing' are commonly used. Strong emphasis is placed on use of supplementary approaches to calibrate metabolite abundance in units of concentration in IMS studies and comparison of IMS results with biochemical data obtained by different methods to help identify potential artifacts.
代谢组学技术包括成像质谱（IMS；也称为质谱成像、MSI 或基质辅助激光解吸/电离质谱成像、MALDI MSI），是评估大脑中许多化合物水平的重要方法，可用于描述脑疾病的代谢表型，并鉴定疾病生物标志物。ATP 是大脑能量代谢的核心物质，而 IMS 研究报告的其在大脑中的异质性分布以及 ATP/ADP 比值的区域差异与早期研究结果不一致。因此，对这些不一致的数据进行了分析，并与使用严格方法保存不稳定代谢物的生化文献进行了比较。在死后缺血期间，快速代谢导致了不均衡的、非常低的局部 ATP 水平和低的 ATP/ADP 比值。分析大脑成分的一个关键方面是其在组织收获期间和之后的稳定性，因此测量浓度与体内的生理水平非常接近。不幸的是，除了神经化学领域之外，冷冻或加热使大脑酶失活的要求并没有得到广泛的认识，而且包括断头、脑切除/解剖和“速冻”在内的不会阻止死后自溶的程序通常被使用。在 IMS 研究中，强烈强调使用补充方法来校准代谢物丰度的浓度单位，并将 IMS 结果与通过不同方法获得的生化数据进行比较，以帮助识别潜在的假象。
