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

## TL;DR

This study uses advanced imaging techniques to map lipid distributions in a mouse model of a neurodegenerative disease, focusing on a toxic lipid linked to the condition.

## Contribution

The study introduces ammonium fluoride electrospray doping in positive ion mode for improved lipid detection in IR-MALDESI MSI.

## Key findings

- Psychosine accumulates in brain regions associated with GLD-related impairments, such as the cerebellum and brain stem.
- Ammonium fluoride doping enhances lipid detection in IR-MALDESI MSI, though with limited success for sphingolipids.
- IR-MALDESI and parallel reaction monitoring confirm the spatial distribution of psychosine in GALC-deficient mouse brains.

## Abstract

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.

The online version contains supplementary material available at 10.1007/s00216-026-06326-3.