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

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• 作者：Do-Wan Lee^a ; ^b ; Yoon-Ki Nam^c ; Tai-Kyung Kim^d ; Jae-Hwa Kim^e ; Sang-Young Kim^a ; ^b ; Jung-Whan Min^f ; Jung-Hoon Lee^a ; ^b ; ^g ; Hwi-Yool Kim^d ; Dai-Jin Kim^e ; ^h ; Bo-Young Choe^a ; ^b ; ^{bychoe@catholic.ac.kr" class="auth_mail}
• 关键词：Ala ; alanine ; ANOVA ; analysis of variance ; Asp ; aspartate ; BALs ; blood-alcohol levels ; CNTL ; controls ; Cr ; creatine ; D2O ; deuterium oxide ; Eth ; ethanol ; GAD ; glutamic acid decarboxylase ; Gln ; glutamine ; Glu ; glutamate ; Glx ; glutamine complex ; GPC ; glycerophosphocholine ; GSH ; glutathione ; HDE ; high-dose-ethanol ; HR-MAS ; high-resolution magic angle spinning ; HSD ; honestly significant difference ; Lac ; lactate ; LDE ; low-dose ethanol ; mIns ; myo-Inositol ; MRS ; magnetic resonance spectroscopy ; NAA ; N-a
• 刊名：Neuroscience
• 出版年：14 March, 2014
• 年：2014
• 卷：262
• 期：Complete
• 页码：107-117
• 全文大小：870 K

文摘

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 8 h for 4 days. 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 (鈭? correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and aspartate (Asp) (+), myo-Inositol (mIns) and Asp (鈭?, mIns and alanine (+), mIns and taurine (+), and mIns and tNAA (鈭?. 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 ¹H 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.