National Institute on Drug Abuse, Bethesda, MD 20892, USA.
Neuroimage. 2013 Jan 1;64:277-83. doi: 10.1016/j.neuroimage.2012.08.057. Epub 2012 Aug 28.
Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also the metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in the thalamus. In contrast, alcohol intoxication caused a significant increase in [1-(11)C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in the cerebellum and the smallest in the thalamus. In heavy alcohol drinkers [1-(11)C]acetate brain uptake during alcohol challenge tended to be higher than in occasional drinkers (p<0.06) and the increases in [1-(11)C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-(11)C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (i.e. ketogenic diets) may have in alcoholics undergoing alcohol detoxification.
酒精中毒会导致大脑葡萄糖代谢明显减少，我们假设这不仅反映了其 GABA 能增强作用，还反映了作为替代大脑能量来源的乙酸盐的代谢。为了验证这一假设，我们分别使用正电子发射断层扫描（PET）评估了酒精中毒对大脑葡萄糖和乙酸盐代谢的影响。我们发现，酒精中毒显著降低了整个大脑的葡萄糖代谢（用 FDG 测量），小脑和枕叶皮质的降幅最大，而丘脑的降幅最小。相比之下，酒精中毒导致[1-(11)C]乙酸盐脑摄取显著增加（以标准摄取值 SUV 测量），小脑的增加最大，而丘脑的增加最小。在重度酒精饮用者中，酒精挑战期间[1-(11)C]乙酸盐脑摄取倾向于高于偶尔饮酒者（p<0.06），并且酒精引起的小脑[1-(11)C]乙酸盐摄取增加与报告的饮酒量呈正相关（r=0.66，p<0.01）。我们的发现证实了在中毒期间大脑葡萄糖代谢的减少，并记录了大脑乙酸盐摄取的增加。观察到的区域大脑代谢减少和区域[1-(11)C]乙酸盐摄取增加之间的相反变化支持了这样一种假设，即在酒精中毒期间，大脑可能依赖乙酸盐作为替代大脑能量来源，并提供了初步证据表明，大量酒精暴露可能促进了乙酸盐作为能量底物的利用。这些发现提出了一个问题，即增加血浆乙酸盐浓度（即生酮饮食）可能对正在进行酒精戒断的酗酒者有潜在的治疗益处。
