Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry
Open Access
- 19 April 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Analytical and Bioanalytical Chemistry
- Vol. 403 (7), 1851-1861
- https://doi.org/10.1007/s00216-012-5988-5
Abstract
Metabolite distribution imaging via imaging mass spectrometry (IMS) is an increasingly utilized tool in the field of neurochemistry. As most previous IMS studies analyzed the relative abundances of larger metabolite species, it is important to expand its application to smaller molecules, such as neurotransmitters. This study aimed to develop an IMS application to visualize neurotransmitter distribution in central nervous system tissue sections. Here, we raise two technical problems that must be resolved to achieve neurotransmitter imaging: (1) the lower concentrations of bioactive molecules, compared with those of membrane lipids, require higher sensitivity and/or signal-to-noise (S/N) ratios in signal detection, and (2) the molecular turnover of the neurotransmitters is rapid; thus, tissue preparation procedures should be performed carefully to minimize postmortem changes. We first evaluated intrinsic sensitivity and matrix interference using Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS) to detect six neurotransmitters and chose acetylcholine (ACh) as a model for study. Next, we examined both single MS imaging and MS/MS imaging for ACh and found that via an ion transition from m/z 146 to m/z 87 in MS/MS imaging, ACh could be visualized with a high S/N ratio. Furthermore, we found that in situ freezing method of brain samples improved IMS data quality in terms of the number of effective pixels and the image contrast (i.e., the sensitivity and dynamic range). Therefore, by addressing the aforementioned problems, we demonstrated the tissue distribution of ACh, the most suitable molecular specimen for positive ion detection by IMS, to reveal its localization in central nervous system tissues.Keywords
This publication has 54 references indexed in Scilit:
- Desorption Electrospray Ionization then MALDI Mass Spectrometry Imaging of Lipid and Protein Distributions in Single Tissue SectionsAnalytical Chemistry, 2011
- Visualization of neuropeptides in paraffin-embedded tissue sections of the central nervous system in the decapod crustacean, Penaeus monodon, by imaging mass spectrometryPeptides, 2011
- Matrix-Assisted Laser Desorption/Ionization Imaging Mass SpectrometryInternational Journal of Molecular Sciences, 2010
- Detection of characteristic distributions of phospholipid head groups and fatty acids on neurite surface by time-of-flight secondary ion mass spectrometryMedical Molecular Morphology, 2010
- Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometryJournal of Lipid Research, 2009
- Magnetic Nanoparticle-Based Mass Spectrometry for the Detection of Biomolecules in Cultured CellsJournal of Nanoscience and Nanotechnology, 2009
- Matrix‐assisted laser desorption/ionization quadrupole ion trap time‐of‐flight (MALDI‐QIT‐TOF)‐based imaging mass spectrometry reveals a layered distribution of phospholipid molecular species in the mouse retinaRapid Communications in Mass Spectrometry, 2008
- Imaging Mass Spectrometry Technology and Application on Ganglioside Study; Visualization of Age-Dependent Accumulation of C20-Ganglioside Molecular Species in the Mouse HippocampusPLOS ONE, 2008
- Mass Imaging and Identification of Biomolecules with MALDI-QIT-TOF-Based SystemAnalytical Chemistry, 2008
- MALDI-MS-based imaging of small molecules and proteins in tissuesCurrent Opinion in Chemical Biology, 2007