Detection and Imaging of Neurotransmitters in Rodent Brain Tissue Using FMP-10 and ZnO Nanoparticle Matrices with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is an analytical technique used to visualize the spatial distribution of molecules within biological samples. In our lab, we employ two complementary matrices, 2-fluoro-1-methyl pyridinium (FMP-10) and zinc oxide nanoparticles (ZnO NP), to image neurotransmitters in rodent brain tissue. FMP-10 facilitates on-tissue chemical derivatization to detect 17 neurochemicals, notably dopamine, γ-aminobutyric acid (GABA), serotonin, and norepinephrine. ZnO NP detects 9 neurochemicals, including glutamate and glutamine, which are undetectable by FMP-10. We applied both matrices to investigate neurochemical changes in male and female adolescent rats administered edible Δ-9-tetrahydrocannabinol (THC). Our MALDI MSI data revealed significant downregulation of dopamine, GABA, glutamate, and glutamine levels in the prefrontal cortex and nucleus accumbens of THC-treated males and females. To improve the quantitative accuracy of our MALDI MSI analysis, we evaluated deuterated GABA (GABA-d6) as an internal standard to achieve precise and reproducible quantitation of molecules.