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Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-3779-3556
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2019 (English)In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 16, no 10, p. 1021-1028Article in journal (Refereed) Published
Abstract [en]

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 mu m. 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 16, no 10, p. 1021-1028
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Analytical Chemistry
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URN: urn:nbn:se:uu:diva-395725DOI: 10.1038/s41592-019-0551-3ISI: 000488225900033PubMedID: 31548706OAI: oai:DiVA.org:uu-395725DiVA, id: diva2:1365308
Funder
Swedish Foundation for Strategic Research , RIF14-0078EU, FP7, Seventh Framework Programme, 607517Swedish Research Council, 2018-03320Swedish Research Council, 2018-05501Swedish Research Council, 2018-05133Available from: 2019-10-24 Created: 2019-10-24 Last updated: 2019-10-24Bibliographically approved

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Shariatgorji, MohammadrezaNilsson, AnnaFridjonsdottir, ElvaVallianatou, TheodosiaSävmarker, JonasOdell, Luke R.Andrén, Per E.

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Shariatgorji, MohammadrezaNilsson, AnnaFridjonsdottir, ElvaVallianatou, TheodosiaSävmarker, JonasBezard, ErwanOdell, Luke R.Andrén, Per E.
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Department of Pharmaceutical BiosciencesScience for Life Laboratory, SciLifeLabPreparative Medicinal Chemistry
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