Differential Sphingolipid and Phospholipid Profiles in Alcohol and Nicotine-Derived Nitrosamine Ketone-Associated White Matter Degeneration.

Abstract

BACKGROUND:

Alcohol-mediated neurodegeneration is associated with white matter (WM) atrophy due to targeting of myelin and oligodendrocytes. However, variability in disease severity suggests cofactors contribute to WM degeneration. We examined the potential cofactor role of the tobacco-specific nitrosamine, nicotine-derived nitrosamine ketone (NNK), because smoking causes WM atrophy and most heavy drinkers consume tobacco products.

METHODS:

This 8-week study of Long Evans rats had 4 treatment groups: control; NNK-2 mg/kg, 3×/wk in weeks 3 to 8; ethanol (EtOH) (chronic-26% caloric + binge-2 g/kg, 3×/wk in weeks 7 to 8); and EtOH + NNK. Exposure effects on WM lipid biochemical profiles and in situ distributions were examined using matrix-assisted laser desorption/ionization imaging mass spectrometry and tandem mass spectrometry.

RESULTS:

NNK mainly caused WM fiber degeneration and fiber loss, EtOH caused demyelination, and dual exposures had additive effects. EtOH and EtOH + NNK decreased WM (including corpus callosum) and/or gray matter (hypothalamus, cortex, medial temporal) levels of several phosphatidylserine, phosphatidylinositol, and sphingolipid (sulfatide [ST]) species, while NNK increased or had minimal effect on these lipids. EtOH + NNK had broader and larger inhibitory effects on phospholipids and ST than EtOH or NNK alone. Principal component analysis clustered control with NNK, and EtOH with EtOH + NNK groups, highlighting the independent EtOH- rather than NNK-driven responses.

CONCLUSIONS:

Chronic EtOH exposures decreased several phospholipid and sphingolipid species in brain, while concomitant NNK exposures exacerbated these effects. These findings support our hypothesis that tobacco smoking is a pathogenic cofactor in alcohol-mediated WM degeneration.

• Authors: Emine B Yalcin, Kavin Nunez, Ming Tong, Suzanne M de la Monte
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 39 Issue 12 Pg. 2324-33 (Dec 2015) ISSN: 1530-0277 [Electronic] England
• PMID: 26756797 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 by the Research Society on Alcoholism.

Chemical References

• Ketones
• Nitrosamines
• Phospholipids
• Sphingolipids
• Ethanol
• Nicotine

Topics

• Animals
• Ethanol (toxicity)
• Ketones (toxicity)
• Nicotine (toxicity)
• Nitrosamines (toxicity)
• Phospholipids (metabolism)
• Rats
• Rats, Long-Evans
• Sphingolipids (metabolism)
• White Matter (drug effects, metabolism, pathology)