IR-MALDESI mass spectrometry imaging of underivatized neurotransmitters in brain tissue of rats exposed to tetrabromobisphenol A
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 USA 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 labeled (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.
KeywordsIR-MALDESI Neurotransmitters Mass spectrometry imaging Exposomics Orbitrap
All mass spectrometry measurements were made in the Molecular Education, Technology, and Research Innovation Center (METRIC) at NC State University. We are grateful for the NIEHS research team who designed and executed the TBBPA exposure portion of this project, especially Suzanne Fenton, Manushree Bharadwaj, Joshua Warmack, and Sagi Enicole Gillera.
This study received financial assistance from the National Institutes of Health grants R01GM087964 (MCB, ME, DM) and P30ES025128 to North Carolina State University as well as a National Institutes of Health IPA Agreement with HP.
Compliance with ethical standards
All aspects of the rat studies were approved by the Institutional Animal Care and Use Committees of NIEHS and NCSU.
Conflict of interest
The authors declare that they have no conflicts of interest
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