Graves Christina L, Norloff Erik, Thompson Darius, Kosyk Oksana, Sang Yingning, Chen Angela, Zannas Anthony S, Wallet Shannon M
Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Carolina Stress Initiative, University of North Carolina School of Medicine, Chapel Hill, NC, 27514, USA.
Brain Behav Immun Health. 2023 Jun 17;31:100655. doi: 10.1016/j.bbih.2023.100655. eCollection 2023 Aug.
Chronic early life stress (ELS) potently impacts the developing central nervous and immune systems and is associated with the onset of gastrointestinal disease in humans. Though the gut-brain axis is appreciated to be a major target of the stress response, the underlying mechanisms linking ELS to gut dysfunction later in life is incompletely understood. Zebrafish are a powerful model validated for stress research and have emerged as an important tool in delineating neuroimmune mechanisms in the developing gut. Here, we developed a novel model of ELS and utilized a comparative transcriptomics approach to assess how chronic ELS modulated expression of neuroimmune genes in the developing gut and brain. Zebrafish exposed to ELS throughout larval development exhibited anxiety-like behavior and altered expression of neuroimmune genes in a time- and tissue-dependent manner. Further, the altered gut neuroimmune profile, which included increased expression of genes associated with neuronal modulation, correlated with a reduction in enteric neuronal density and delayed gut transit. Together, these findings provide insights into the mechanisms linking ELS with gastrointestinal dysfunction and highlight the zebrafish model organism as a valuable tool in uncovering how "the body keeps the score."
慢性早期生活应激（ELS）对发育中的中枢神经系统和免疫系统有强大影响，并与人类胃肠道疾病的发生有关。尽管肠-脑轴被认为是应激反应的主要靶点，但ELS与后期肠道功能障碍之间的潜在机制仍未完全了解。斑马鱼是一种经过应激研究验证的强大模型，已成为阐明发育中肠道神经免疫机制的重要工具。在这里，我们开发了一种新型的ELS模型，并采用比较转录组学方法来评估慢性ELS如何调节发育中肠道和大脑中神经免疫基因的表达。在整个幼体发育过程中暴露于ELS的斑马鱼表现出类似焦虑的行为，并以时间和组织依赖性方式改变神经免疫基因的表达。此外，肠道神经免疫特征的改变，包括与神经元调节相关基因的表达增加，与肠神经元密度降低和肠道转运延迟相关。这些发现共同为ELS与胃肠道功能障碍之间的机制提供了见解，并突出了斑马鱼模式生物作为揭示“身体如何记分”的有价值工具。
