title: Dose-dependent influence of short-term intermittent ethanol intoxication on cerebral neurochemical changes in rats detected by ex vivo proton nuclear magnetic resonance spectroscopy.
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.
authors.affiliation: 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.
authors.forename: Do-Wan
authors.initials: DW
authors.lastname: Lee
authors.affiliation: NMR Research Team & Life Science Group, Agilent Technologies Korea Ltd., #966-5 Daechi-dong, Gangnam-gu, Seoul 135-848, Republic of Korea.
authors.forename: Yoon-Ki
authors.initials: YK
authors.lastname: Nam
authors.affiliation: Department of Veterinary Surgery, Konkuk University, #120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Tai-Kyung
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, The Catholic University of Korea, College of Medicine, #505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Jae-Hwa
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Sang-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Radiological Science, The Shingu University College of Korea, Geumgwang 2-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-743, Republic of Korea.
authors.forename: Jung-Whan
authors.initials: JW
authors.lastname: Min
authors.affiliation: 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.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Veterinary Surgery, Konkuk University, #120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Hwi-Yool
authors.initials: HY
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Dai-Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Choe
mesh_terms: D000409:Alanine / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001835:Body Weight; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D013654:Taurine; D001224:Aspartic Acid; D000431:Ethanol; D007294:Inositol; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D005978:Glutathione; D000409:Alanine
keywords: brain; frontal cortex; high-resolution spectra; intermittent ethanol intoxication; metabolites