Spatially resolved lipids in a mouse brain model of globoid cell leukodystrophy via IR-MALDESI MSI and parallel reaction monitoring MSI.

Globoid cell leukodystrophy (GLD) is a genetic neurodegenerative disease caused by mutations in galactosylceramide β-galactosidase (GALC) that results in the accumulation of the cytotoxic sphingolipid, psychosine. As psychosine is a biomarker specific to GLD, identifying the most afflicted regions of the nervous system can assist in better understanding the disease mechanism. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) and parallel reaction monitoring were utilized to elucidate the spatial distribution of the psychosine analyte and confirm the identity of the ion in a sagittal section of a GALC-deficient mouse brain. The presence of the psychosine was increased in specific anatomical regions of the brain responsible for the bodily functions that are impaired by GLD (cerebellum and brain stem). Several electrospray solvent additives (dopants) have enhanced the detection of various analyte types but with little success in enhancing the detection of sphingolipids. This study investigates the usefulness of ammonium fluoride electrospray doping in the positive ion mode for lipidomic IR-MALDESI MSI analysis.

Duke Scholars

Author Anthony J Filiano Neurosurgery