Pang Xuechao, Gao Shanshan, Ga Man, Zhang Jin, Luo Zhigang, Chen Yanhua, Zhang Ruiping, He Jiuming, Abliz Zeper
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Centre for Imaging & Systems Biology, Minzu University of China, Beijing 100081, China.
Anal Chem. 2021 May 4;93(17):6746-6754. doi: 10.1021/acs.analchem.1c00467. Epub 2021 Apr 23.
Metabolic networks and their dysfunction in the brain are closely associated with central nervous function and many psychogenic diseases. Thus, it is of utmost importance to develop a high-throughput imaging method for metabolic network mapping. Here, we developed a metabolic network mapping method to discover the metabolic contexts and alterations with spatially resolved information from the microregion of the brain by ambient-air flow-assisted desorption electrospray ionization mass spectrometry imaging and metabolomics analysis, which can be performed without any chemical derivatization, labels, or complex sample pretreatment. This method can map hundreds of different polar functional metabolites involved in multiple metabolic pathways, including not only neurotransmitters but also purines, organic acids, polyamines, cholines, and carbohydrates, in the rat brain. These high-coverage metabolite profile and microregional distribution information constitute complex networks that regulate advanced functions in the central nervous system. Moreover, this methodology was further used to discover not only the dysregulated metabolites but also the brain microregions involved in the pathology of a scopolamine-treated Alzheimer's model. Furthermore, this methodology was demonstrated to be a powerful visualizing tool that could offer novel insight into the metabolic events and provide spatial information about these events in central nervous system diseases.
大脑中的代谢网络及其功能障碍与中枢神经功能和许多精神性疾病密切相关。因此，开发一种用于代谢网络图谱绘制的高通量成像方法至关重要。在此，我们开发了一种代谢网络图谱绘制方法，通过环境气流辅助解吸电喷雾电离质谱成像和代谢组学分析，从大脑微区获取具有空间分辨信息的代谢背景和变化情况，该方法无需任何化学衍生、标记或复杂的样品预处理即可进行。此方法能够绘制大鼠大脑中数百种参与多种代谢途径的不同极性功能代谢物，这些代谢物不仅包括神经递质，还包括嘌呤、有机酸、多胺、胆碱和碳水化合物。这些高覆盖度的代谢物谱和微区分布信息构成了调节中枢神经系统高级功能的复杂网络。此外，该方法不仅进一步用于发现东莨菪碱处理的阿尔茨海默病模型病理学中失调的代谢物，还用于发现涉及的脑微区。此外，该方法被证明是一种强大的可视化工具，可为代谢事件提供新的见解，并在中枢神经系统疾病中提供有关这些事件的空间信息。
