A Lipidomics Atlas of Selected Sphingolipids in Multiple Mouse Nervous System Regions

Abstract

Many lipids, including sphingolipids, are essential components of the nervous system. Sphingolipids play critical roles in maintaining the membrane structure and integrity and in cell signaling. We used a multi-dimensional mass spectrometry-based shotgun lipidomics platform to selectively analyze the lipid species profiles of ceramide, sphingomyelin, cerebroside, and sulfatide; these four classes of sphingolipids are found in the central nervous system (CNS) (the cerebrum, brain stem, and spinal cord) and peripheral nervous system (PNS) (the sciatic nerve) tissues of young adult wild-type mice. Our results revealed that the lipid species profiles of the four sphingolipid classes in the different nervous tissues were highly distinct. In addition, the mRNA expression of sphingolipid metabolism genes—including the ceramidase synthases that specifically acylate the N-acyl chain of ceramide species and sphingomyelinases that cleave sphingomyelins generating ceramides—were analyzed in the mouse cerebrum and spinal cord tissue in order to better understand the sphingolipid profile differences observed between these nervous tissues. We found that the distinct profiles of the determined sphingolipids were consistent with the high selectivity of ceramide synthases and provided a potential mechanism to explain region-specific CNS ceramide and sphingomyelin levels. In conclusion, we portray for the first time a lipidomics atlas of select sphingolipids in multiple nervous system regions and believe that this type of knowledge could be very useful for better understanding the role of this lipid category in the nervous system.

UPLC-Q-Exactive Orbitrap-MS-Based Untargeted Lipidomic Analysis of Lipid Molecular Species in Spinal Cords from Different Domesticated Animals

“…In contrast, PE was abundant more than PC in white matter [28][29][30]. More specifically, the SM species containing very long-chain fatty acids were found in high abundance in young wild-type C57BL/6 male mice [8], consistent with our findings in the spinal cords of domesticated animals. Furthermore, the correlation analysis of the lipidomic and genome data demonstrated the importance of PC, PE, TAG, HexCer-NS and SM.…”

“…Given that the spinal cord acts as a pivotal neural conduit for transmitting signals between the peripheral nervous system and the brain, the role of lipids within this context is especially significant. Previous research has documented that lipids are indispensable biomolecules for neurodevelopment, particularly in the formation of myelin [8]. Furthermore, disruptions in lipid metabolism within spinal cords have been linked to a spectrum of neurological disorders [9,10].…”