Abstract
Glycosphingolipids (GSLs) are amphipathic lipids composed of a sphingoid base and a fatty acyl attached to a saccharide moiety. GSLs play an important role in signal transduction, directing proteins within the membrane, cell recognition, and modulation of cell adhesion. Gangliosides and sulfatides belong to a group of acidic GSLs, and numerous studies report their involvement in neurodevelopment, aging, and neurodegeneration. In this study, we used an approach based on hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution tandem mass spectrometry (HRMS/MS) to characterize the glycosphingolipid profile in rat brain tissue. Then, we screened characterized lipids aiming to identify changes in glycosphingolipid profiles in the normal aging process and tau pathology. Thorough screening of acidic glycosphingolipids in rat brain tissue revealed 117 ganglioside and 36 sulfatide species. Moreover, we found two ganglioside subclasses that were not previously characterized—GT1b-Ac2 and GQ1b-Ac2. The semi-targeted screening revealed significant changes in the levels of sulfatides and GM1a gangliosides during the aging process. In the transgenic SHR24 rat model for tauopathies, we found elevated levels of GM3 gangliosides which may indicate a higher rate of apoptotic processes.
Highlights
The central nervous system is known for its high lipid content and complexity
Gangliosides and sulfatides belong to a group of acidic GSLs, and numerous studies report their involvement in neurodevelopment, aging, and neurodegeneration
A total number of 117 ganglioside species belonging to 19 major subclasses and 36 sulfatide species were positively identified in rat brain tissue (Table S1)
Summary
Still little is known about its precise role in cells. Glycosphingolipids (GSLs) are amphipathic lipids composed of a sphingoid base and a fatty acyl group attached to a mono-, or oligosaccharide moiety [1]. GSLs are located mainly in the outer leaflet of the plasmatic membrane. The hydrophobic fatty acyl and sphingoid base are anchored in the membrane while the saccharide sticks out of the cell surface. GSLs are not homogeneously layered within the membrane, rather they are grouped with functional proteins and cholesterol in lipid rafts. Their main functions are modulation of signal transduction and directing proteins to specific places within the membrane [2]. The glycan part on the outer side of the membrane can be recognized by glycanbinding proteins and antibodies, and bacteria and viruses [3]
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