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探索急性应激后小脑代谢组学特征。

Exploring the metabolomic profile of cerebellum after exposure to acute stress.

机构信息

Department of Pharmacy, Section of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens (NKUA), Athens, Greece.

Department of Biological Applications and Technology, Laboratory of Biochemistry, School of Health Sciences, University of Ioannina, Ioannina, Greece.

出版信息

Stress. 2021 Nov;24(6):952-964. doi: 10.1080/10253890.2021.1973997. Epub 2021 Sep 23.

Abstract

Psychological stress and stress-related disorders constitute a major health problem in modern societies. Although the brain circuits involved in emotional processing are intensively studied, little is known about the implication of cerebellum in stress responses whereas the molecular changes induced by stress exposure in cerebellum remain largely unexplored. Here, we investigated the effects of acute stress exposure on mouse cerebellum. We used a forced swim test (FST) paradigm as an acute stressor. We then analyzed the cerebellar metabolomic profiles of stressed ( = 11) versus control ( = 11) male CD1 mice by a Nuclear Magnetic Resonance (NMR)-based, untargeted metabolomics approach. Our results showed altered levels of 19 out of the 47 annotated metabolites, which are implicated in neurotransmission and N-acetylaspartic acid (NAA) turnover, as well as in energy and purine/pyrimidine metabolism. We also correlated individual metabolite levels with FST behavioral parameters, and reported associations between FST readouts and levels of 4 metabolites. This work indicates an altered metabolomic signature after acute stress in the cerebellum and highlights a previously unexplored involvement of cerebellum in stress responses.

摘要

心理压力和与压力相关的障碍是现代社会的一个主要健康问题。尽管涉及情绪处理的大脑回路受到了深入研究,但小脑在应激反应中的作用知之甚少,而应激暴露诱导的小脑内分子变化在很大程度上仍未得到探索。在这里,我们研究了急性应激暴露对小鼠小脑的影响。我们使用强迫游泳测试 (FST) 范式作为急性应激源。然后,我们通过基于核磁共振 (NMR) 的非靶向代谢组学方法分析了应激 ( = 11) 与对照 ( = 11) 雄性 CD1 小鼠小脑的代谢组学图谱。我们的结果显示,在神经递质传递和 N-乙酰天冬氨酸 (NAA) 周转以及能量和嘌呤/嘧啶代谢中,47 种注释代谢物中有 19 种的水平发生了改变。我们还将个体代谢物水平与 FST 行为参数相关联,并报告了 FST 读数与 4 种代谢物水平之间的关联。这项工作表明小脑在急性应激后出现代谢组学特征改变,并强调了小脑在应激反应中以前未被探索的作用。

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