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

  • M. Caleb Bagley
  • Måns Ekelöf
  • Kylie Rock
  • Heather Patisaul
  • David C. Muddiman
Research Paper

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 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.

Keywords

IR-MALDESI Neurotransmitters Mass spectrometry imaging Exposomics Orbitrap 

Notes

Acknowledgements

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.

Funding information

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

Supplementary material

216_2018_1420_MOESM1_ESM.pdf (3.4 mb)
ESM 1 (PDF 3448 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • M. Caleb Bagley
    • 1
  • Måns Ekelöf
    • 1
  • Kylie Rock
    • 2
    • 3
  • Heather Patisaul
    • 2
    • 3
  • David C. Muddiman
    • 1
    • 3
    • 4
  1. 1.FTMS Laboratory for Human Health Research, Department of ChemistryNorth Carolina State UniversityRaleighUSA
  2. 2.Department of Biological SciencesNorth Carolina State UniversityRaleighUSA
  3. 3.Center for Human Health and the EnvironmentNorth Carolina State UniversityRaleighUSA
  4. 4.Molecular Education, Technology and Research Innovation Center (METRIC)North Carolina State UniversityRaleighUSA

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