Cholesterol and phospholipids in frontal cortex and synaptosomes of suicide completers: relationship with endosomal lipid trafficking genes

J Psychiatr Res. 2013 Feb;47(2):272-9. doi: 10.1016/j.jpsychires.2012.10.019. Epub 2012 Nov 16.

Abstract

Cholesterol (CHL) and phospholipid (PL) levels in synaptosomal membranes in particular can have an impact on cell signalling. Alterations in peripheral CHL measures have been consistently reported in suicidal behaviour. As CHL and PL turnover in the brain are important in synapse maintenance and function, the objective of this study was to determine if differences exist in synaptosomal cholesterol and phospholipid levels between suicide completers and controls. Expression measures of genes involved in lipid trafficking suggest an association between Lysosomal acid lipase A, cholesteryl ester hydrolase (LIPA) and brain PL levels, with LIPA being significantly increased in violent suicides and associated with alterations in brain PL. The results of this study suggest an altered PL content mediated by LIPA expression in violent suicides in the prefrontal cortex, which would have important consequences for inhibitory neurotransmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Analysis of Variance
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Case-Control Studies
  • Cholesterol
  • Endosomes
  • Female
  • Frontal Lobe / metabolism
  • Frontal Lobe / ultrastructure*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins / genetics
  • LDL-Receptor Related Proteins / metabolism
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Microscopy, Electron, Transmission
  • Niemann-Pick C1 Protein
  • Phospholipids / metabolism*
  • Statistics, Nonparametric
  • Sterol Esterase / genetics
  • Sterol Esterase / metabolism*
  • Suicide*
  • Synaptosomal-Associated Protein 25 / metabolism
  • Synaptosomes / metabolism*
  • Syntaxin 1 / metabolism

Substances

  • Actins
  • Adaptor Proteins, Vesicular Transport
  • Apolipoproteins E
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • NPC1 protein, human
  • Niemann-Pick C1 Protein
  • Phospholipids
  • SNAP25 protein, human
  • SORL1 protein, human
  • STX1A protein, human
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Cholesterol
  • LIPA protein, human
  • Sterol Esterase
  • sortilin