Simultaneous quantification of dopamine, serotonin, their metabolites and amino acids by LC-MS/MS in mouse brain following repetitive transcranial magnetic stimulation

Eugenia Z Poh; Dorothee Hahne; Jessica Moretti; Alan R Harvey; Michael W Clarke; Jennifer Rodger

doi:10.1016/j.neuint.2019.104546

Simultaneous quantification of dopamine, serotonin, their metabolites and amino acids by LC-MS/MS in mouse brain following repetitive transcranial magnetic stimulation

Neurochem Int. 2019 Dec:131:104546. doi: 10.1016/j.neuint.2019.104546. Epub 2019 Sep 10.

Authors

Eugenia Z Poh¹, Dorothee Hahne², Jessica Moretti³, Alan R Harvey⁴, Michael W Clarke⁵, Jennifer Rodger⁶

Affiliations

¹ School of Biological Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; School of Human Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Australia. Electronic address: eugenia.poh@research.uwa.edu.au.
² Metabolomics Australia, Centre for Microscopy, Characterisation and Analysis, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia. Electronic address: dorothee.hahne@gmail.com.
³ School of Biological Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; School of Human Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Australia. Electronic address: jessica.moretti@research.uwa.edu.au.
⁴ School of Human Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Australia. Electronic address: alan.harvey@uwa.edu.au.
⁵ Metabolomics Australia, Centre for Microscopy, Characterisation and Analysis, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia. Electronic address: michael.clarke@uwa.edu.au.
⁶ School of Biological Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; School of Human Sciences, University of Western Australia, 35 Stirling Highway, Crawley, 6009, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Australia. Electronic address: jennifer.rodger@uwa.edu.au.

PMID: 31518601
DOI: 10.1016/j.neuint.2019.104546

Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) is a form of non-invasive brain stimulation that has shown therapeutic potential for various nervous system disorders. In addition to its modulatory effects on neuronal excitability, rTMS is capable of altering neurotransmitter (e.g., glutamate, GABA, dopamine and serotonin) concentrations in cortical and subcortical brain regions. Here we used a modified liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) to quantify changes in 27 free amino acids and the monoamines: dopamine (DA), serotonin (5HT) and their metabolites (DOPAC, HVA; 5HIAA) in the mouse brain. Awake C57BL/6 J mice (either sex, 8-12 weeks old) received 10 Hz rTMS using two devices that can deliver low (LI-; 12 mT; custom built) or high (Fo8-; 1.2 T; MagVenture) intensity rTMS. Sham (unstimulated) mice were used as controls. Samples were collected immediately following a single session of rTMS or sham and processed for LC-MS/MS. The modified LC-MS/MS method used to detect DA, 5-HT and their metabolites showed good accuracy and precision with regression coefficients greater than 0.999, and an intra- and inter-day reproducibility with values < 13%. Fo8-rTMS induced a significant reduction in cortical 5-HT turnover rates, hippocampal DOPAC and an increase in striatal DOPAC concentrations. Fo8-rTMS also reduced concentrations of hippocampal α-aminoadipic acid, and striatal serine, threonine, sarcosine, aspartate and glutamate. There were no changes in the level of any compounds following LI-rTMS as compared to sham. The rapid change in monoamine turnover and amino acid concentrations following Fo8-rTMS but not LI-rTMS suggests that different stimulation parameters recruit different cellular mechanisms related to rTMS-induced plasticity. The described method can be used for the characterisation of trace levels of neurotransmitters and amino acids in brain tissue homogenates, providing a useful and precise tool to investigate localised neurotransmitter changes in animal models of health and disease.

Keywords: Amino acid; LC-MS/MS; Neurotransmitter; Repetitive transcranial magnetic stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / analysis*
Amino Acids / metabolism*
Animals
Brain Chemistry / radiation effects*
Calibration
Cerebral Cortex / metabolism
Cerebral Cortex / radiation effects
Chromatography, High Pressure Liquid
Dopamine / analysis*
Dopamine / metabolism*
Female
Hippocampus / metabolism
Hippocampus / radiation effects
Male
Mice
Mice, Inbred C57BL
Neostriatum / metabolism
Neostriatum / radiation effects
Reproducibility of Results
Serotonin / analysis*
Serotonin / metabolism*
Tandem Mass Spectrometry
Transcranial Magnetic Stimulation*

Substances

Amino Acids
Serotonin
Dopamine