Comprehensive mapping of neurotransmitter networks by MALDI–MS imaging
Nat Methods. 2019-09-23; 16(10): 1021-1028
DOI: 10.1038/s41592-019-0551-3
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Shariatgorji M(1)(2), Nilsson A(1)(2), Fridjonsdottir E(1), Vallianatou T(1),Källback P(1), Katan L(3), Sävmarker J(3), Mantas I(4), Zhang X(4), BezardE(5)(6), Svenningsson P(4), Odell LR(7), Andrén PE(8)(9).
Author information:
(1)Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences,Uppsala University, Uppsala, Sweden.
(2)Science for Life Laboratory, National Resource for Mass Spectrometry Imaging,Uppsala University, Uppsala, Sweden.
(3)Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
(4)Section of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
(5)Institut des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux, France.
(6)Institut des Maladies Neurodégénératives, CNRS, Bordeaux, France.
(7)Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
(8)Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
(9)Science for Life Laboratory, National Resource for Mass Spectrometry Imaging, Uppsala University, Uppsala, Sweden.
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
PMID: 31548706