Alcohol hangover induces mitochondrial dysfunction and free radical production in mouse cerebellum.

KARADAYIAN, A.G.; BUSTAMANTE, J.; CZERNICZYNIEC, A.; LOMBARDI, P.; CUTRERA, R.A.; LORES-ARNAIZ, S.

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2015 vol. 304 p. 47 - 59

0306-4522

Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when 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 (3.8 g/kg BW) or saline solution. Mitochondrial function was evaluated 6 hours after injection (AH onset). At the onset of alcohol hangover, malateglutamate 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 NO metabolism, 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 alcohol hangover involves mitochondrial dysfunction in mouse cerebellum showing the long lasting effects of acute EtOH exposure in the central nervous system.