Chronic ethanol consumption profoundly alters regional brain ceramide and sphingomyelin content in rodents

ACS Chem Neurosci. 2015 Feb 18;6(2):247-59. doi: 10.1021/cn500174c. Epub 2014 Dec 1.

Abstract

Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 μm spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol.

Keywords: Ceramide; alcohol; lipids; mass spectrometry imaging; matrix implanted laser desorption ionization; matrix-assisted laser desorption ionization; silver nanoparticles; sphingomyelin.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alcohol Drinking / metabolism
  • Animals
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / metabolism*
  • Central Nervous System Depressants / administration & dosage*
  • Ceramides / metabolism*
  • Ethanol / administration & dosage*
  • Male
  • Metal Nanoparticles
  • Mice, Inbred C57BL
  • Silver Compounds
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Sphingomyelins / metabolism*
  • White Matter / drug effects
  • White Matter / growth & development
  • White Matter / metabolism

Substances

  • Central Nervous System Depressants
  • Ceramides
  • Silver Compounds
  • Sphingomyelins
  • Ethanol