Karadayian A G, Bustamante J, Czerniczyniec A, Lombardi P, Cutrera R A, Lores-Arnaiz S
Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
Instituto de Fisiología y Biofísica Bernardo Houssay, Facultad de Medicina, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
Neuroscience. 2015 Sep 24;304:47-59. doi: 10.1016/j.neuroscience.2015.07.012. Epub 2015 Jul 17.
Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when ethanol (EtOH) is absent in plasma. Previous data indicate that AH induces mitochondrial dysfunction and free radical production in mouse brain cortex. The aim of this work was to study mitochondrial function and reactive oxygen species production in mouse cerebellum at the onset of AH. Male mice received a single i.p. injection of EtOH (3.8g/kg BW) or saline solution. Mitochondrial function was evaluated 6h after injection (AH onset). At the onset of AH, malate-glutamate and succinate-supported state 4 oxygen uptake was 2.3 and 1.9-fold increased leading to a reduction in respiratory control of 55% and 48% respectively, as compared with controls. Decreases of 38% and 16% were found in Complex I-III and IV activities. Complex II-III activity was not affected by AH. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Mitochondrial membrane potential and permeability were decreased by AH in cerebellum mitochondria. Together with this, AH induced a 25% increase in superoxide anion and a 92% increase in hydrogen peroxide production in cerebellum mitochondria. Related to nitric oxide (NO) metabolism, neuronal nitric oxide synthase (nNOS) protein expression was 52% decreased by the hangover condition compared with control group. No differences were found in cerebellum NO production between control and treated mice. The present work demonstrates that the physiopathological state of AH involves mitochondrial dysfunction in mouse cerebellum showing the long-lasting effects of acute EtOH exposure in the central nervous system.
酒精宿醉（AH）被定义为在类似暴饮酒精后出现的一种暂时状态，始于血浆中乙醇（EtOH）消失之时。先前的数据表明，酒精宿醉会诱发小鼠大脑皮层的线粒体功能障碍和自由基产生。这项研究的目的是在酒精宿醉开始时，研究小鼠小脑的线粒体功能和活性氧的产生。雄性小鼠腹腔注射一次EtOH（3.8g/kg体重）或生理盐水。在注射后6小时（酒精宿醉开始时）评估线粒体功能。与对照组相比，在酒精宿醉开始时，苹果酸-谷氨酸和琥珀酸支持的状态4氧摄取分别增加了2.3倍和1.9倍，导致呼吸控制分别降低了55%和48%。复合体I-III和IV的活性分别下降了38%和16%。复合体II-III的活性不受酒精宿醉的影响。通过流式细胞术评估线粒体膜电位和线粒体通透性变化。酒精宿醉使小脑线粒体的膜电位和通透性降低。与此同时，酒精宿醉使小脑线粒体中的超氧阴离子增加了25%，过氧化氢的产生增加了92%。与一氧化氮（NO）代谢相关，与对照组相比，宿醉状态使神经元型一氧化氮合酶（nNOS）蛋白表达降低了52%。在对照组和处理组小鼠的小脑中，NO的产生没有差异。目前的研究表明，酒精宿醉的生理病理状态涉及小鼠小脑的线粒体功能障碍，显示了急性乙醇暴露对中枢神经系统的长期影响。
