IR-MALDESI mass spectrometry imaging of underivatized neurotransmitters in brain tissue of rats exposed to tetrabromobisphenol A

Abstract

There is a pressing need to develop tools for assessing possible neurotoxicity, particularly for chemicals where the mode of action is poorly understood. Tetrabromobisphenol a (TBBPA), a highly abundant brominated flame retardant, has lately been targeted for neurotoxicity analysis by concerned public health entities in the EU and United States because it is a suspected thyroid disruptor and neurotoxicant. In this study, infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to a Q Exactive Plus mass spectrometer was used for the analysis of neurotransmitters in the brains of rats exposed to TBBPA in gestation and lactation through their mothers. Three neurotransmitters of interest were studied in three selected regions of the brain; caudate putamen, substantia nigra (SN) and dorsal raphe. Stable Isotope Labelled (SIL) standards were used as internal standards and a means to achieve relative quantification. This study serves as a demonstration of a new application of IR-MALDESI, namely that neurotransmitter distributions can be confidently and rapidly imaged without derivatization.

Streamlined Multimodal DESI and MALDI Mass Spectrometry Imaging on a Singular Dual-Source FT-ICR Mass Spectrometer

“…Application of ambient MSI has been applied hundreds of times to faster scanning FT-Orbitrap platforms or to hybrid FT-ICR MS that accumulate ions externally within a multipole or ion traps [42][43][44][45]. In contrast, few reports exist of DESI imaging being applied to FT-ICR on commercial instrumentation; one report utilized a fully automated machined DESI source previously mentioned on a past generation of Bruker Daltonics instrumentation after recoding FlexImaging to control the DESI stage, instead of the MALDI on the commercial instrument allowing for a broad array of ambient sources to be applied [46].…”

Spatially Resolved Mass Spectrometry at the Single Cell: Recent Innovations in Proteomics and Metabolomics

“… 163 Agtuca et al explored the metabolic asymmetry between infected and noninfected soybean nodules with LAESI where elevated fatty acid, purine, and lipid levels occurred as a result of Bradyrhizobium japonicum infection. 164 The Muddiman group used ice matrices to increase lipid yields, 165 explored dynamic neurotransmitter imaging, 166 used IR-MALDESI for imaging metabolomics in plant and mammalian samples, 167 , 168 and coupled a drift tube for ion mobility direct collision cross section (CCS) measurements from several tissue types. 169 Most recently, cell-to-cell lipid heterogeneity in a dispersed HeLa cell culture was demonstrated by Xing et al with IR-MALDESI.…”

Applications of stable isotopes in MALDI imaging: current approaches and an eye on the future

“…While MALDI-IMS was first applied to the analysis of fresh-frozen tissue, recent tissue preparation advances have allowed useful information to be generated from chemically fixed tissues as well [74]. SIL compound use for quantitation has also been demonstrated in each type of tissue [75,76]. For example, the neurotoxicity of tetrabromobisphenol (TBBPA), a prevalent flame retardant used in a variety of consumer goods, has been investigated using infrared MALDI electrospray ionisation (IR-MALDESI) IMS [75].…”