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

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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.

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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

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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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Authors and Affiliations

  1. Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL, 32827, USA

    Chunyan Wang, Miao Wang & Xianlin Han

  2. Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Yunhua Zhou

  3. Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Jeffrey L. Dupree

Authors
  1. Chunyan Wang
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  2. Miao Wang
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  3. Yunhua Zhou
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  4. Jeffrey L. Dupree
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  5. Xianlin Han
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Correspondence to Xianlin Han.

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Wang, C., Wang, M., Zhou, Y. et al. Alterations in Mouse Brain Lipidome after Disruption of CST Gene: A Lipidomics Study. Mol Neurobiol 50, 88–96 (2014). https://doi.org/10.1007/s12035-013-8626-0

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  • DOI: https://doi.org/10.1007/s12035-013-8626-0

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