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

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

Author information

1
Department of Biomedical Engineering, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea; Research Institute of Biomedical Engineering, The Catholic University of Korea, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
2
NMR Research Team & Life Science Group, Agilent Technologies Korea Ltd., #966-5 Daechi-dong, Gangnam-gu, Seoul 135-848, Republic of Korea.
3
Department of Veterinary Surgery, Konkuk University, #120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
4
Department of Biomedical Science, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
5
Department of Radiological Science, The Shingu University College of Korea, Geumgwang 2-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-743, Republic of Korea.
6
Department of Biomedical Engineering, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea; Research Institute of Biomedical Engineering, The Catholic University of Korea, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea; Department of Radiology, Kyunghee Medical Center, #23 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-872, Republic of Korea.
7
Department of Biomedical Science, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea; Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
8
Department of Biomedical Engineering, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea; Research Institute of Biomedical Engineering, The Catholic University of Korea, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea. Electronic address: bychoe@catholic.ac.kr.

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

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