Dose-dependent influence of short-term intermittent ethanol intoxication on cerebral neurochemical changes in rats detected by ex vivo proton nuclear magnetic resonance spectroscopy

Neuroscience. 2014 Mar 14:262:107-17. doi: 10.1016/j.neuroscience.2013.12.061. Epub 2014 Jan 7.

Abstract

The aim of this study was to quantitatively assess the effects of short-term intermittent ethanol intoxication on cerebral metabolite changes among sham controls (CNTL), low-dose ethanol (LDE)-exposed, and high-dose ethanol (HDE)-exposed rats, which were determined with ex vivo high-resolution spectra. Eight-week-old male Wistar rats were divided into three groups. Twenty rats in the LDE (n=10) and the HDE (n=10) groups received ethanol doses of 1.5 and 2.5 g/kg, respectively, through oral gavage every 8h for 4days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz ¹H nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the three groups). Normalized total N-acetylaspartate (tNAA: NAA+NAAG [N-acetylaspartyl-glutamate]), GABA, and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The six pairs of normalized metabolite levels were positively (+) or negatively (-) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and aspartate (Asp) (+), myo-Inositol (mIns) and Asp (-), mIns and alanine (+), mIns and taurine (+), and mIns and tNAA (-). Our results suggested that short-term intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo(1)H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of short-term intermittent ethanol intoxication in the frontal cortex.

Keywords: brain; frontal cortex; high-resolution spectra; intermittent ethanol intoxication; metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / metabolism
  • Alcoholic Intoxication / metabolism*
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Body Weight
  • Central Nervous System Depressants / pharmacology*
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism*
  • Glutathione / pharmacology
  • Inositol / metabolism
  • Male
  • Nuclear Magnetic Resonance, Biomolecular
  • Rats
  • Rats, Wistar
  • Taurine / metabolism
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Central Nervous System Depressants
  • Taurine
  • Aspartic Acid
  • Ethanol
  • Inositol
  • gamma-Aminobutyric Acid
  • N-acetylaspartate
  • Glutathione
  • Alanine