Alterations in Mouse Brain Lipidome after Disruption of CST Gene: A Lipidomics Study
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To investigate the effects of a critical enzyme, cerebroside sulfotransferase (CST), involving sulfatide biosynthesis on lipid (particularly sphingolipid) homeostasis, herein, we determined the lipidomes of brain cortex and spinal cord from CST null and heterozygous (CST−/− and CST+/−, respectively) mice in comparison to their wild-type littermates by multi-dimensional mass spectrometry-based shotgun lipidomics. As anticipated, we demonstrated the absence of sulfatide in the tissues from CST−/− mice and found that significant reduction of sulfatide mass levels was also present, but in an age-dependent manner, in CST+/− mice. Unexpectedly, we revealed that the profiles of sulfatide species in CST+/− mice were significantly different from that of littermate controls with an increase in the composition of species containing saturated and hydroxylated fatty acyl chains. Contrary to the changes of sulfatide levels, shotgun lipidomics analysis did not detect significant changes of the mass levels of other lipid classes examined. Taken together, shotgun lipidomics analysis demonstrated anticipated sulfatide mass deficiency in CST defect mouse brain and revealed novel brain lipidome homeostasis in these mice. These results might provide new insights into the role of CST in myelin function.
KeywordsAlzheimer’s disease Cerebroside sulfotransferase Neurolipidome Shotgun lipidomics Sphingolipidomics Sulfatide
Central nervous system
Acyl chain containing m carbons and n double bonds
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Multi-dimensional mass spectrometry-based shotgun lipidomics
Polymerase chain reaction
This work was supported by National Institute on Aging Grant R01 AG31675 and intramural institutional research funds. Special thanks are expressed to Dr. Juan Pablo Palavicini for his contribution to genotyping, Ms. Jacina Redden and Nicole Harris for their skillful technical support in the analysis of lipids and/or animal care, and Ms. Imee Tiu for her editorial assistance.
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