Lipidomics reveals dysfunctional glycosynapses in schizophrenia and the G72/G30 transgenic mouse

Schizophr Res. 2014 Nov;159(2-3):365-9. doi: 10.1016/j.schres.2014.08.029. Epub 2014 Sep 26.

Abstract

Background: Abnormal structural/functional connectivity has been proposed to underlie the pathophysiology of schizophrenia. However, the biochemical basis of abnormal connectivity remains undefined.

Methods: We undertook a shotgun lipidomic analysis of over 700 lipids across 26 lipid subclasses in the frontal cortex of schizophrenia subjects and hippocampus of G72/G30 transgenic mice.

Results: We demonstrate that glycosphingolipids and choline plasmalogens, structural lipid pools in myelin, are significantly elevated in the frontal cortex obtained from patients suffering from schizophrenia and the hippocampus of G72/G30 transgenic mice.

Conclusions: Our data suggest that structural lipid alterations in oligodendrocyte glycosynapses are responsible for dysconnectivity in schizophrenia and that increased expression of G72 protein may play a role in the development of abnormal glycosynapses.

Keywords: Dysconnectivity; Glycosynapse; Plasmalogens; Schizophrenia; Sulfatides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carrier Proteins / genetics*
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease*
  • Glycosphingolipids / metabolism
  • Hippocampus / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Linkage Disequilibrium
  • Lipid Metabolism / genetics
  • Lipids / genetics
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Schizophrenia / genetics*
  • Schizophrenia / pathology*

Substances

  • Carrier Proteins
  • DAOA protein, human
  • Glycosphingolipids
  • Intracellular Signaling Peptides and Proteins
  • Lipids