Description:
<jats:sec><jats:title>Background</jats:title><jats:p>Chronic alcohol consumption leads to oxidative stress in a variety of cells, especially in brain cells because they have a reduced oxidative metabolism of alcohol. Uncoupling proteins (<jats:styled-content style="fixed-case">UCP</jats:styled-content>s) are anion channels of the inner mitochondrial membrane, which can decouple internal respiration. “Mild uncoupling” of the mitochondrial respiratory chain leads to a reduced production of free radicals (reactive oxygen species) and a reduction in oxidative cell stress. The extent to which chronic alcohol consumption regulates UCP‐2 and ‐4 in the brain is still unknown.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We examined the effects of a 12‐week 5% alcohol diet in the brain of male <jats:styled-content style="fixed-case">W</jats:styled-content>istar rats (<jats:italic>n </jats:italic>=<jats:italic> </jats:italic>34). Cerebral gene and protein expression of <jats:styled-content style="fixed-case">UCP</jats:styled-content>‐2, ‐4, as well as <jats:styled-content style="fixed-case">B</jats:styled-content>cl‐2, and the release of cytochrome <jats:italic>c</jats:italic> out of the mitochondria were detected by real‐time polymerase chain reaction and <jats:styled-content style="fixed-case">W</jats:styled-content>estern blot analysis. The percentage of degenerated cells was determined by <jats:styled-content style="fixed-case">F</jats:styled-content>luoro–<jats:styled-content style="fixed-case">J</jats:styled-content>ade <jats:styled-content style="fixed-case">B</jats:styled-content> staining of brain slices.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Brains of rats with a chronic alcohol diet showed an increased gene and protein expression of <jats:styled-content style="fixed-case">UCP</jats:styled-content>‐2 and ‐4. The expression of the antiapoptotic protein <jats:styled-content style="fixed-case">B</jats:styled-content>cl‐2 in the brain of the alcohol‐treated animals was decreased significantly, whereas cytochrome <jats:italic>c</jats:italic> release from mitochondria was increased. In addition increased neurodegeneration could be demonstrated in the alcohol‐treated animals.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Chronic alcohol consumption leads to a cerebral induction of <jats:styled-content style="fixed-case">UCP</jats:styled-content>‐2 and ‐4 with a simultaneous decrease in the antiapoptotic protein <jats:styled-content style="fixed-case">B</jats:styled-content>cl‐2, cytochrome <jats:italic>c</jats:italic> release from mitochondria and increased neurodegeneration. This study reveals a compensatory effect of <jats:styled-content style="fixed-case">UCP</jats:styled-content>‐2 and ‐4 in the brain during chronic alcohol consumption.</jats:p></jats:sec>