2023 FDA Science Forum
MALDI IMS identified changes in lipids and metabolites in rat brains following arsenic exposure
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Contributing OfficeNational Center for Toxicological Research
Abstract
Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) is a label free, ever-evolving technology, which produces 2D ion density maps representing the distribution of an analyte (s) across a tissue section. Correlation of MALDI images with H&E or immunohistochemistry (IHC) stained serial sections (IHC) provides a “molecular map” to assess an analyte’s location and relative intensity to in relation to specific cell types and/or tissue architecture. Although this mass spectrometry (MS)-based approach was initially developed to analyze larger analytes such as proteins and peptides, the recent incorporation of high-resolution instruments such as the Fourier- transform ion cyclotron resonance (FTICR) mass spectrometer within imaging workflows has increased the number of detectable analytes making identification of lipids, n-linked glycans and small molecule metabolites feasible. MALDI IMS use across toxicity studies has been on the rise, specifically in neurotoxicology targeting specific brain abnormalities or changes due to exposure to toxic materials or drugs. A recent study at NCTR was conducted to determine the effects of exposure to inorganic arsenic on development utilized MALDI IMS to gain a more thorough understanding or potential toxicity effects on the brain. Brain tissue from Sprague-Dawley rats at postnatal day 21 and adult tissues were analyzed with the adult animals representing long-term effects. Four arsenic treatment groups were tested: 0, 0.10, 1.50, and 3.75 mg/kg/day with a maximum 3-4/sex/treatment group. Dose dependent changes or markers of toxicity and their distribution to specific brain regions were assessed in relation to histopathology. Interestingly, MALDI IMS identified many lipids which have been linked to arsenic exposure in mice including phosphatidylcholines of varying chain length including: PC (36:1) PC (40:5) and PC (38:6). These studies are ongoing but the preliminary data showing distribution of lipids and metabolites in relation to arsenic exposure will be presented.
