title: Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry.
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.
authors.affiliation: Biomolecular Imaging and Proteomics, National Resource for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124 Uppsala, Sweden.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shariatgorji
authors.affiliation: AstraZeneca, Drug Safety and Metabolism, Cambridge CB4 0WG, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Strittmatter
authors.affiliation: Biomolecular Imaging and Proteomics, National Resource for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124 Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.affiliation: Biomolecular Imaging and Proteomics, National Resource for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124 Uppsala, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Källback
authors.affiliation: Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Alvarsson
authors.affiliation: Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Biomolecular Imaging and Proteomics, National Resource for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124 Uppsala, Sweden.
authors.forename: Theodosia
authors.initials: T
authors.lastname: Vallianatou
authors.affiliation: Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.affiliation: AstraZeneca, Drug Safety and Metabolism, Cambridge CB4 0WG, UK.
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Goodwin
authors.affiliation: 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.
authors.forename: Per E
authors.initials: PE
authors.lastname: Andren
mesh_terms: D000465:Algorithms; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D018377:Neurotransmitter Agents; D011619:Psychotropic Drugs
keywords: Dopamine; Imaging; Mass spectrometry; Neurotransmitter; Parkinson's disease; Serotonin