Molecular Neurobiology

, Volume 50, Issue 1, pp 88–96 | Cite as

Alterations in Mouse Brain Lipidome after Disruption of CST Gene: A Lipidomics Study

  • Chunyan Wang
  • Miao Wang
  • Yunhua Zhou
  • Jeffrey L. Dupree
  • Xianlin Han
Article

Abstract

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.

Keywords

Alzheimer’s disease Cerebroside sulfotransferase Neurolipidome Shotgun lipidomics Sphingolipidomics Sulfatide 

Abbreviations

AD

Alzheimer’s disease

CBS

Cerebroside

Cer

Ceramide

CNS

Central nervous system

CST

Cerebroside sulfotransferase

ESI

Electrospray ionization

Het

Heterozygous

KO

Knockout

m:n

Acyl chain containing m carbons and n double bonds

MALDI-TOF/MS

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

MDMS-SL

Multi-dimensional mass spectrometry-based shotgun lipidomics

PC

Choline glycerophospholipid

PCR

Polymerase chain reaction

SD

Statistical deviation

SM

Sphingomyelin

WT

Wild type

Notes

Acknowledgments

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Chunyan Wang
    • 1
  • Miao Wang
    • 1
  • Yunhua Zhou
    • 2
  • Jeffrey L. Dupree
    • 3
  • Xianlin Han
    • 1
  1. 1.Diabetes and Obesity Research CenterSanford-Burnham Medical Research InstituteOrlandoUSA
  2. 2.Department of Anatomy, Histology and Embryology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of Anatomy and NeurobiologyVirginia Commonwealth UniversityRichmondUSA

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