Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging.
Mohammadreza ShariatgorjiAnna NilssonElva FridjonsdottirTheodosia VallianatouPatrik KällbackLuay KatanJonas SävmarkerIoannis MantasXiaoqun ZhangErwan BezardPer SvenningssonLuke R OdellPer E AndrenPublished in: Nature methods (2019)
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.
Keyphrases
- high resolution
- mass spectrometry
- resting state
- white matter
- immune response
- cerebral ischemia
- ms ms
- endothelial cells
- functional connectivity
- multiple sclerosis
- high performance liquid chromatography
- single molecule
- capillary electrophoresis
- fluorescence imaging
- high density
- photodynamic therapy
- blood brain barrier
- sensitive detection