BackgroundAlcohol abuse affects the brain regions responsible for memory, coordination and emotional processing. Binge alcohol drinking has shown reductions in brain activity, but the molecular targets have not been completely elucidated. We hypothesized that brain cells respond to excessive alcohol by releasing a novel inflammatory mediator, called cold inducible RNA-binding protein (CIRP), which is critical for the decreased brain metabolic activity and impaired cognition.MethodsMale wild type (WT) mice and mice deficient in CIRP (CIRP−/−) were studied before and after exposure to binge alcohol level by assessment of relative brain glucose metabolism with fluorodeoxyglucose (18FDG) and positron emission tomography (PET). Mice were also examined for object-place memory (OPM) and open field (OF) tasks.ResultsStatistical Parametric Analysis (SPM) of 18FDG-PET uptake revealed marked decreases in relative glucose metabolism in distinct brain regions of WT mice after binge alcohol. Regional analysis (post hoc) revealed that while activity in the temporal (secondary visual) and limbic (entorhinal/perirhinal) cortices was decreased in WT mice, relative glucose metabolic activity was less suppressed in the CIRP−/− mice. Group and condition interaction analysis revealed differing responses in relative glucose metabolism (decrease in WT mice but increase in CIRP−/− mice) after alcohol in brain regions including the hippocampus and the cortical amygdala where the percent changes in metabolic activity correlated with changes in object discrimination performance. Behaviorally, alcohol-treated WT mice were impaired in exploring a repositioned object in the OPM task, and were more anxious in the OF task, whereas CIRP−/− mice were not impaired in these tasks.ConclusionCIRP released from brain cells could be responsible for regional brain metabolic hypoactivity leading to cognitive impairment under binge alcohol conditions.

中文翻译：

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细胞外冷诱导RNA结合蛋白介导小鼠酗酒引起的大脑活动减退和认知受损


背景酒精滥用会影响负责记忆、协调和情绪处理的大脑区域。大量饮酒会导致大脑活动减少，但其分子靶标尚未完全阐明。我们假设脑细胞通过释放一种称为冷诱导 RNA 结合蛋白 (CIRP) 的新型炎症介质来对过量酒精做出反应，该介质对于大脑代谢活动减少和认知受损至关重要。 方法雄性野生型 (WT) 小鼠和缺陷小鼠通过使用氟脱氧葡萄糖 (18FDG) 和正电子发射断层扫描 (PET) 评估相对脑葡萄糖代谢，研究了暴露于酗酒之前和之后的 CIRP (CIRP−/−)。还检查了小鼠的物体位置记忆 (OPM) 和开放视野 (OF) 任务。结果 18FDG-PET 摄取的统计参数分析 (SPM) 显示，狂饮​​酒精后 WT 小鼠不同大脑区域的相对葡萄糖代谢显着下降。区域分析（事后）显示，虽然 WT 小鼠的颞叶（次级视觉）和边缘（内嗅/鼻周）皮质活动减少，但 CIRP−/− 小鼠的相对葡萄糖代谢活动受到较少抑制。组和条件相互作用分析揭示了酒精后大脑区域（包括海马体和皮质杏仁​​核）相对葡萄糖代谢的不同反应（WT 小鼠减少，但 CIRP−/− 小鼠增加），其中代谢活动的百分比变化与物体的变化相关歧视表现。在行为上，酒精治疗的WT小鼠在OPM任务中探索重新定位的物体时受到损害，并且在OF任务中更加焦虑，而CIRP−/−小鼠在这些任务中没有受到损害。结论 脑细胞释放的 CIRP 可能是导致局部脑代谢低下的原因，导致酗酒条件下的认知障碍。