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自愿 binge-patterned 酒精摄入和性别特异性对小鼠肠道和大脑中单胺相关神经化学特征的影响。

Voluntary binge-patterned alcohol drinking and sex-specific influences on monoamine-related neurochemical signatures in the mouse gut and brain.

机构信息

Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.

Department of Veterinary Microbiology and Preventative Medicine, Iowa State University, Ames, IA, USA.

出版信息

Alcohol Clin Exp Res. 2021 May;45(5):996-1012. doi: 10.1111/acer.14592. Epub 2021 May 7.

Abstract

BACKGROUND

Altered monoamine (i.e., serotonin, dopamine, and norepinephrine) activity following episodes of alcohol abuse plays key roles not only in the motivation to ingest ethanol, but also physiological dysfunction related to its misuse. Although monoamine activity is essential for physiological processes that require coordinated communication across the gut-brain axis (GBA), relatively little is known about how alcohol misuse may affect monoamine levels across the GBA. Therefore, we evaluated monoamine activity across the mouse gut and brain following episodes of binge-patterned ethanol drinking.

METHODS

Monoamine and select metabolite neurochemical concentrations were analyzed by ultra-high-performance liquid chromatography in gut and brain regions of female and male C57BL/6J mice following "Drinking in the Dark" (DID), a binge-patterned ethanol ingestion paradigm.

RESULTS

First, we found that alcohol access had an overall small effect on gut monoamine-related neurochemical concentrations, primarily influencing dopamine activity. Second, neurochemical patterns between the small intestine and the striatum were correlated, adding to recent evidence of modulatory activity between these areas. Third, although alcohol access robustly influenced activity in brain areas in the mesolimbic dopamine system, binge exposure also influenced monoaminergic activity in the hypothalamic region. Finally, sex differences were observed in the concentrations of neurochemicals within the gut, which was particularly pronounced in the small intestine.

CONCLUSION

Together, these data provide insights into the influence of alcohol abuse and biological sex on monoamine-related neurochemical changes across the GBA, which could have important implications for GBA function and dysfunction.

摘要

背景

酒精滥用后单胺(即 5-羟色胺、多巴胺和去甲肾上腺素)活性的改变不仅在摄取乙醇的动机中起关键作用,而且与酒精滥用相关的生理功能障碍也有关。虽然单胺活性对于需要跨肠-脑轴(GBA)进行协调通讯的生理过程至关重要,但关于酒精滥用如何影响 GBA 中单胺水平的信息相对较少。因此,我们评估了 binge 样饮酒后小鼠肠道和大脑中的单胺活性。

方法

通过超高效液相色谱法分析雌性和雄性 C57BL/6J 小鼠在“暗饮”(DID),即 binge 样乙醇摄入范式后肠道和大脑区域中的单胺和选定代谢物神经化学浓度。

结果

首先,我们发现酒精摄入对肠道单胺相关神经化学浓度有总体的小影响,主要影响多巴胺活性。其次,小肠和纹状体之间的神经化学模式相关,增加了这些区域之间调节活性的最新证据。第三,尽管酒精摄入强烈影响中脑边缘多巴胺系统中的脑区活动,但 binge 暴露也影响了下丘脑区域的单胺能活性。最后,在肠道内神经化学物质的浓度中观察到性别差异,在小肠中尤为明显。

结论

这些数据共同提供了关于酒精滥用和生物性别对 GBA 中单胺相关神经化学变化的影响的见解,这可能对 GBA 的功能和功能障碍有重要意义。

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