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咖啡因引发的斑马鱼性别特异性焦虑样行为和生理反应。

Zebrafish gender-specific anxiety-like behavioral and physiological reactions elicited by caffeine.

作者信息

Li Yaxi, Yan Zhi, Lu Zhen, Li Ke

机构信息

Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.

Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; School of Ocean, Yantai University, Yantai 264005, China.

出版信息

Behav Brain Res. 2024 Aug 24;472:115151. doi: 10.1016/j.bbr.2024.115151. Epub 2024 Jul 15.

DOI:10.1016/j.bbr.2024.115151
PMID:39019091
Abstract

Caffeine exerts a biphasic effect on zebrafish behavior. High doses of caffeine have been associated with increased stress and anxiety, whereas low doses have been found to enhance performance on tasks requiring focus and attention. However, the sex-specific nature of these biphasic effects on behavior and physiology remains unclear. This study assessed the behavioral responses and hormone levels in male and female zebrafish after acute exposure to caffeine ranging from 0.3 to 600 mg/L. The results showed no significant difference in caffeine intake between males and females after acute exposure at each concentration. Caffeine-induced behavioral and physiological responses indicated a threshold dosage existed between 30 and 300 mg/L. Female fish displayed increased anxiety-like behavioral phenotypes, i.e., latency to upper and freezing, whereas males exhibited more erratic movement following acute exposure to a high-dose treatment. In addition, females exhibited a significant increase in whole-body cortisol levels, while males experienced a testosterone elevation at 300 mg/L of caffeine acute exposure. There was a significant decrease in the duration of erratic movements in males treated with the androgen receptor antagonist flutamide compared to the control group. The transcriptome analysis uncovered 511 and 592 up-regulated and 761 and 922 down-regulated differential expression genes in males and females, respectively, compared to the control. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis revealed that caffeine has the potential to impact various pathways in zebrafish, including phototransduction and steroid hormone biosynthesis. Our findings demonstrate that testosterone and cortisol play a combined role in regulating stress responses in both behavior and physiology. Furthermore, our study highlights the significance of encompassing both male and female zebrafish as a model system.

摘要

咖啡因对斑马鱼的行为具有双相效应。高剂量咖啡因与压力和焦虑增加有关,而低剂量则被发现可提高需要专注和注意力的任务表现。然而,这些行为和生理双相效应的性别特异性本质仍不清楚。本研究评估了雄性和雌性斑马鱼在急性暴露于0.3至600 mg/L咖啡因后的行为反应和激素水平。结果表明,在每个浓度下急性暴露后,雄性和雌性之间的咖啡因摄入量没有显著差异。咖啡因诱导的行为和生理反应表明,在30至300 mg/L之间存在一个阈值剂量。雌性鱼表现出焦虑样行为表型增加,即向上游动潜伏期和僵住,而雄性在急性暴露于高剂量处理后表现出更不稳定的运动。此外,雌性鱼全身皮质醇水平显著升高,而雄性在300 mg/L咖啡因急性暴露时睾酮水平升高。与对照组相比,用雄激素受体拮抗剂氟他胺处理的雄性鱼不稳定运动的持续时间显著减少。转录组分析发现,与对照组相比,雄性和雌性分别有511个和592个上调以及761个和922个下调的差异表达基因。京都基因与基因组百科全书(KEGG)和基因本体论(GO)通路分析表明,咖啡因有可能影响斑马鱼的各种通路,包括光转导和类固醇激素生物合成。我们的研究结果表明,睾酮和皮质醇在调节行为和生理应激反应中起联合作用。此外,我们的研究强调了将雄性和雌性斑马鱼作为模型系统的重要性。

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