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Quantitative assessment of neurochemical changes in a rat model of long-term alcohol consumption as detected by in vivo and ex vivo proton nuclear magnetic resonance spectroscopy
Authors:Do-Wan Lee  Sang-Young Kim  Jae-Hwa Kim  Taehyeong Lee  Changbum Yoo  Yoon-Ki Nam  Jin-Young Jung  Hae-Chung Shin  Hwi-Yool Kim  Dai-Jin Kim  Bo-Young Choe
Affiliation:1. Department of Biomedical Engineering, The Catholic University of Korea, College of Medicine, Seoul, South Korea;2. Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul, South Korea;3. Department of Biomedical Science, The Catholic University of Korea, College of Medicine, Seoul, South Korea;4. Department of Veterinary Surgery, Konkuk University of Korea, Seoul, South Korea;5. NMR Research Team & Life Science Group, Agilent Technologies Korea Ltd., Seoul, South Korea;6. Department of Psychiatry, Seoul St. Mary’s Hospital, The Catholic University of Korea, College of Medicine, Seoul, South Korea
Abstract:The aim of present study was to quantitatively investigate the neurochemical profile of the frontal cortex region in a rat model of long-term alcohol consumption, by using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T and ex vivo1H high-resolution magic angle spinning (HR-MAS) technique at 11.7 T. Twenty male rats were divided into two groups and fed a liquid diet for 10 weeks. After 10 weeks, in vivo1H MRS spectra were acquired from the frontal cortex brain region. After in vivo1H MRS experiments, all animals were sacrificed and 20 frontal cortex tissue samples were harvested. All tissue examinations were performed with the 11.7 T HR-MAS spectrometer and high-resolution spectra were acquired. The in vivo and ex vivo spectra were quantified as absolute metabolite concentrations and normalized ratios of total signal-intensity (i.e., metabolitesNorm), respectively. The absolute quantifications of in vivo spectra showed significantly higher glycerophosphocholine plus phosphocholine (GPC + PCh) and lower myo-inositol (mIns) concentrations in ethanol-treated rats compared to controls. The quantifications of ex vivo spectra showed significantly higher PChNorm, ChoNorm and tChoNorm, and lower GPCNorm and mInsNorm ratio levels in ethanol-treated rats compared to controls. Our findings suggest that reduced mIns concentrations caused by the long-term alcohol consumption may lead to hypo-osmolarity syndrome and astrocyte hyponatremia. In addition, increased choline-containing compound concentrations may reflect an increased cell turnover rate of phosphatidylcholine and other phospholipids, indicating an adaptive mechanism. Therefore, these results might be utilized as key markers in chronic alcohol intoxication metabolism.
Keywords:MRS, magnetic resonance spectroscopy   NMRS, nuclear magnetic resonance spectroscopy   HR-MAS, high-resolution magic angle spinning   ppm, part per million   CPMG, Carr-Purcell-Meiboom-Gill   CRLB, Cramé  r&ndash  Rao lower bound   LCModel, Linear Combination Model   %SD, percentage standard deviation   Ala, Alanine   Act, acetate   Asp, aspartate   Cho, choline (free choline)   Cr, creatine   PCr, phosphocreatine   tCr, Cr + PCr   GABA, gamma-aminobutyric acid   Gln, glutamine   Glu, glutamate   Glc, glucose   GPC, glycerophosphocholine   GSH, glutathione   sI, scyllo-inositol   mI, myo-inositol   Lac, lactate   NAA, N-acetylaspartate   NAAG, N-acetylaspartylglutamate   tNAA, NAA + NAAG   PCh, phosphocholine   tCho, Cho + PCh + GPC   Eth, ethanol   Tau, taurine   BALs, blood alcohol levels
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