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Neuroimage. 2016 Aug 1;136:129-38. doi: 10.1016/j.neuroimage.2016.05.004. Epub 2016 May 4.

Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry.

Author information

1
Biomolecular Imaging and Proteomics, National Resource for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124 Uppsala, Sweden.
2
AstraZeneca, Drug Safety and Metabolism, Cambridge CB4 0WG, UK.
3
Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
4
Biomolecular Imaging and Proteomics, National Resource for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124 Uppsala, Sweden. Electronic address: per.andren@farmbio.uu.se.

Abstract

With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, serotonin, glutamate, glutamine, aspartate, γ-aminobutyric acid, adenosine) as well as neuroactive drugs (amphetamine, sibutramine, fluvoxamine) and drug metabolites in situ directly in brain tissue sections. The use of both positive and negative ionization modes increased the number of identified molecular targets. Chemical derivatization by charge-tagging the primary amines of molecules significantly increased the sensitivity, enabling the detection of low abundant neurotransmitters and other neuroactive substances previously undetectable by MSI. The sensitivity of the imaging approach of neurochemicals has a great potential in many diverse applications in fields such as neuroscience, pharmacology, drug discovery, neurochemistry, and medicine.

KEYWORDS:

Dopamine; Imaging; Mass spectrometry; Neurotransmitter; Parkinson's disease; Serotonin

[Indexed for MEDLINE]

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