Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization

Abstract

Small molecule neurotransmitters are essential for the function of the nervous system, and neurotransmitter imbalances are often connected to neurological disorders. The ability to quantify such imbalances is important to provide insights into the biochemical mechanisms underlying the disorder. This proof-of-principle study presents online quantification of small molecule neurotransmitters, specifically acetylcholine, γ-aminobutyric acid (GABA) and glutamate, in rat brain tissue sections using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging. By incorporating deuterated internal standards in the nano-DESI solvent we show identification, accurate mapping, and quantification of these small neurotransmitters in rat brain tissue without introducing any additional sample preparation steps. We find that GABA is about twice as abundant in the medial septum-diagonal band complex (MSDB) as in the cortex, while glutamate is about twice as abundant in the cortex as compared to the MSDB. The study shows that nano-DESI is well suited for imaging of small molecule neurotransmitters in health and disease.

High Spatial Resolution Imaging of Mouse Pancreatic Islets Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

“…17–19 Moreover, addition of selected standards to the nano-DESI solvent may be used to compensate for signal variations caused by matrix effects and perform accurate quantification of lipids and metabolites in complex samples. 20–22 We recently introduced an approach for robust nano-DESI MSI with high spatial resolution by adding a shear force probe, which enables precise control of the distance between the sample and nano-DESI probe. 19,23 Herein, we used this approach for imaging of pancreatic islets with high spatial resolution.…”

Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging

“…DESI-MSI is being increasingly used within academia and industry as a reliable and robust imaging technique26. Quantitative DESI-MSI has still to be extensively compared to other techniques such as LC-MS/MS and MALDI-MSI but several groups have reported positive quantitative measurements22. Adjacent sections to those run by LESA-MSI were used to repeat the analysis using DESI-MSI analysis (Fig.…”

“…Other reported techniques employ the use of internal standards to normalize differences in ionization efficiency across tissue sections2021. Quantitative methods have also been published for nano-DESI-MSI22 based on similar techniques as those employed in MALDI-MSI.…”

Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights

“…33 This sample protocol can also be applied to sections used in DESI experiments (applying prior to analysis), or standards can be added directly to the DESI extraction solvent for inclusion in sample analysis. 2 …”

“…Otherwise, the molecule can be identified based on its intact mass by accurate mass matching to databases of known molecules within a certain mass error range. 2,3 …”