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Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

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D Lee

Do-Wan Lee, Sang-Young Kim , Kyu-Ho Song , Bo-Young Choe* , Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea


SU-E-I-34 Sunday 3:00PM - 6:00PM Room: Exhibit Hall

The first goal of this study was to determine the influence of the dose₋dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low₋ and high₋dose₋ethanol₋exposed rats with ex vivo high₋resolution spectra. The second goal of this study was to determine the correlations between the metabolite₋metabolite levels (pairs₋of₋metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats.

Eight₋week₋old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8₋h for 4 days. At the end of the 4₋day intermittent ethanol exposure, one₋dimensional ex vivo 500₋MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups).

Normalized total₋N-acetylaspartate (tNAA: NAA ₊ NAAG [N-acetylaspartyl₋glutamate]), gamma-aminobutyric acid (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 6 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 repeated 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 1H high₋resolution₋magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose₋dependent influence of repeated intermittent ethanol intoxication in the frontal cortex.

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