Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging.

Nature methods (2019-09-25)
Mohammadreza Shariatgorji, Anna Nilsson, Elva Fridjonsdottir, Theodosia Vallianatou, Patrik Källback, Luay Katan, Jonas Sävmarker, Ioannis Mantas, Xiaoqun Zhang, Erwan Bezard, Per Svenningsson, Luke R Odell, Per E Andrén
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3,4-dihydroxyphenylacetone, 95%
Sigma-Aldrich
9-Anthraceneboronic acid, ≥95.0%