Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Phospholipid Changes in a Drosophila Model of Early Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a degenerative disease caused by motor neuron damage in the central nervous system, and it is difficult to diagnose early. Drosophila melanogaster is widely used to investigate disease mechanisms and discover biomarkers because it is easy to induce disease in Drosophila through genetic engineering. We performed matrixassisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to investigate changes in phospholipid distribution in the brain tissue of an ALS-induced Drosophila model. Fly brain tissues of several hundred micrometers or less were sampled using a fly collar to obtain reproducible tissue sections of similar sizes. MSI of brain tissues of Drosophila cultured for 1 or 10 days showed that the distribution of phospholipids, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylserine (PS), and phosphatidylinositol (PI), was significantly different between the control group and the ALS group. In addition, the lipid profile according to phospholipids differed as the culture time increased from 1 to 10 days. These results suggest that disease indicators based on lipid metabolites can be discovered by performing MALDI-MSI on very small brain tissue samples from the Drosophila disease model to ultimately assess the phospholipid changes that occur in early-stage ALS.

Investigation of Phospholipid Differences in Valproic Acid-Induced Autistic Mouse Model Brain Using Mass Spectrometry Imaging

“…To perform MALDI-MSI, 1,5-diaminonaphthalene (1,5-DAN), a matrix optimized for phospholipid detection, was applied to dried tissue sections [ 21 ]. Matrix deposition was performed using a custom-made sublimation apparatus composed of a top and bottom quartz glass chamber, an O-ring, and a clamp.…”

Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-dependent neurodegeneration

“…Interestingly, untargeted lipidomics done in plasma from ALS patients identified significant changes in pathways involved in energy metabolism, including fatty acid metabolism 84 . Other publications also reported lipid changes and altered lipid metabolism in several models of ALS and identified these changes as potential contributors to the disease 78,[85][86][87][88][89] . Finally, histone deacetylase (HDAC) inhibitors, recently investigated as a potential therapeutics in ALS, has been shown to mitigate lipid metabolism alterations in the spinal cord of symptomatic FUS mice 88,90 .…”

DBDA Matrix Increases Ion Abundance of Fatty Acids and Sulfatides in MALDI-TOF and Mass Spectrometry Imaging Studies

“…One such class of biomolecules, lipids, which are critical in cellular structure integrity, signaling, and energy storage have been analyzed broadly using MALDI MSI strategies. For example, fresh frozen bone samples have been imaged resulting in the discovery of unique signatures associated with bone marrow and soft tissues, and phospholipids have been mapped in a Drosophila model of amyotrophic lateral sclerosis brain tissue . Other examples include lipid mapping in cancer models, ischemic stroke, and of the human retina …”

“…For example, fresh frozen bone samples have been imaged resulting in the discovery of unique signatures associated with bone marrow and soft tissues, 1 and phospholipids have been mapped in a Drosophila model of amyotrophic lateral sclerosis brain tissue. 2 Other examples include lipid mapping in cancer models, 3 ischemic stroke, 4 and of the human retina. 5 Despite some common physiochemical properties of lipids, they are a class of biomolecules that are generally quite diverse.…”