Chronic early life stress alters the neuroimmune profile and functioning of the developing zebrafish gut

Christina L Graves; Erik Norloff; Darius Thompson; Oksana Kosyk; Yingning Sang; Angela Chen; Anthony S Zannas; Shannon M Wallet

doi:10.1016/j.bbih.2023.100655

Chronic early life stress alters the neuroimmune profile and functioning of the developing zebrafish gut

Brain Behav Immun Health. 2023 Jun 17:31:100655. doi: 10.1016/j.bbih.2023.100655. eCollection 2023 Aug.

Authors

Christina L Graves^{1

2}, Erik Norloff¹, Darius Thompson¹, Oksana Kosyk³, Yingning Sang¹, Angela Chen¹, Anthony S Zannas^{3

4

2}, Shannon M Wallet¹

Affiliations

¹ Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
² Carolina Stress Initiative, University of North Carolina School of Medicine, Chapel Hill, NC, 27514, USA.
³ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.

Abstract

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."

Keywords: Anxiety; Chronic stress; Early life stress; Gut; Neuroimmune; Zebrafish.