Quantitative assessment of neurochemical changes in a rat model of long-term alcohol consumption as detected byin vivoandex vivoproton nuclear magnetic resonance spectroscopy

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Abstract

Highlights

★ We quantitatively assessed neurochemical profile of long-term alcohol exposed rats. ★ We present first measurements of in vivo and ex vivo data in frontal cortex of rats. ★ Myo-inositol and choline-compound levels were statistically altered in rat brain. ★ Altered neurochemical profile provides useful information in chronic alcoholism. ★ Our findings might be utilized as key-markers in chronic alcoholism-related disorder.

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.

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