近日，瑞典乌普萨拉大学的Per E. Andrén和Luke R. Odell等研究人员合作利用MALDI-MS成像对神经递质网络进行了综合测绘。2019年9月23日，国际知名学术期刊《自然—方法学》在线发表了这一成果。

研究人员提出了一种质谱成像（MSI）方法，用于特定大脑区域中神经递质网络的全面测绘。研究人员开发的反应性基质可促进包含酚羟基和/或伯胺或仲胺基团的分子（包括多巴胺能和血清素能神经递质及其相关代谢物）的共价标记。这些基质改善了对低丰度神经递质的基质辅助激光解吸/电离（MALDI）-MSI检测极限，并有助于以10μm的横向分辨率同时对大脑精细结构中的神经递质进行成像。

研究人员展示了使用反应性基质的固有化学选择性和溴化反应性基质的独特同位素模式识别未知分子种类的策略。研究人员证明了该方法对来自人类尸体组织和动物模型的帕金森病脑样本分析的实用性。因此，神经递质系统的直接成像提供了一种探索各种神经疾病如何通过神经递质调节来影响特定大脑区域的方法。

附：英文原文

Title: Comprehensive mapping of neurotransmitter networks by MALDI–MS imaging

Author: Mohammadreza Shariatgorji, Anna Nilsson, Elva Fridjonsdottir, Theodosia Vallianatou, Patrik Kllback, Luay Katan, Jonas Svmarker, Ioannis Mantas, Xiaoqun Zhang, Erwan Bezard, Per Svenningsson, Luke R. Odell, Per E. Andrn

Issue&Volume: 2019-09-23

Abstract: 

We present a mass spectrometry imaging (MSI) approach for the comprehensive mapping of neurotransmitter networks in specific brain regions. Our fluoromethylpyridinium-based reactive matrices facilitate the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups, including dopaminergic and serotonergic neurotransmitters and their associated metabolites. These matrices improved the matrix-assisted laser desorption/ionization (MALDI)–MSI detection limit toward low-abundance neurotransmitters and facilitated the simultaneous imaging of neurotransmitters in fine structures of the brain at a lateral resolution of 10 µm. We demonstrate strategies for the identification of unknown molecular species using the innate chemoselectivity of the reactive matrices and the unique isotopic pattern of a brominated reactive matrix. We illustrate the capabilities of the developed method on Parkinsonian brain samples from human post-mortem tissue and animal models. The direct imaging of neurotransmitter systems provides a method for exploring how various neurological diseases affect specific brain regions through neurotransmitter modulation.

DOI: 10.1038/s41592-019-0551-3

Source:https://www.nature.com/articles/s41592-019-0551-3