Elsevier

Psychoneuroendocrinology

Volume 92, June 2018, Pages 1-12
Psychoneuroendocrinology

Psychoneuroimmunology and immunopsychiatry of zebrafish

https://doi.org/10.1016/j.psyneuen.2018.03.014Get rights and content

Highlights

  • Despite the high prevalence, neuropsychiatric disorders remain poorly understood.

  • Zebrafish (Danio rerio) are increasingly utilized as a powerful model organism in biomedical research.

  • Zebrafish are a useful tool to study neuro-immune mechanisms and their interplay.

  • Here, we emphasize the growing utility of zebrafish models in translational immunopsychiatry research.

Abstract

Despite the high prevalence of neural and immune disorders, their etiology and molecular mechanisms remain poorly understood. As the zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in biomedical research, mounting evidence suggests these fish as a useful tool to study neural and immune mechanisms and their interplay. Here, we discuss zebrafish neuro-immune mechanisms and their pharmacological and genetic modulation, the effect of stress on cytokines, as well as relevant models of microbiota-brain interplay. As many human brain diseases are based on complex interplay between the neural and the immune system, here we discuss zebrafish models, as well as recent successes and challenges, in this rapidly expanding field. We particularly emphasize the growing utility of zebrafish models in translational immunopsychiatry research, as they improve our understanding of pathogenetic neuro-immune interactions, thereby fostering future discovery of potential therapeutic agents.

Section snippets

Introduction: zebrafish as a model for biomedical research

A small teleost fish, the zebrafish (Danio rerio) has rapidly become a promising model organism in biomedicine, as a low-cost and genetically tractable vertebrate species with high physiological and genetic homology to humans (Kalueff et al., 2014a, Kalueff et al., 2014b). Zebrafish morphology is strikingly similar to rodents, including general macro-organization of various organs, tissues and cell subtypes (Kalueff et al., 2014b). Like in humans, stress in zebrafish is mediated by

Immune cell types and biomarkers in zebrafish

Zebrafish possess a well-developed immune system (Novoa and Figueras, 2012; Renshaw and Trede, 2012; Santoriello and Zon, 2012), coltrolling innate immune responses as the non-specific defense against pathogens. Since zebrafish develop ex-utero, their immune system can be examined from early ontogenesis (Brugman, 2016) (when they solely rely on the innate immune system), thus fostering studies of innate immune processes in the absence of adaptive, antigen-mediated immunity (Brugman, 2016). The

The role of cytokines in the brain

As already mentioned, cytokines play a critical role in tissue growth, differentiation, homeostasis and repair (Foti, 2017). In humans, cytokines have a profound impact on the neuropsychiatric status of individuals (Dantzer, 2017; Yarlagadda et al., 2009). Brain cytokines are produced by microglia (Nimmerjahn et al., 2005), astrocytes (Norden et al., 2016) and vascular endothelium (Wagnerova et al., 2002). In the peripheral nervous system, cytokines are produced by resident or activated

CNS disease models in zebrafish

Zebrafish models can be widely used to address important neuroscience questions. For example, embryonic zebrafish is a useful system to examine the role of cytokines in early neurodevelopment (Weber et al., 2017). The macrophage migration inhibitory factor (MIF) is a neurotrophic cytokine essential for zebrafish inner ear hair cell development and statoacoustic ganglion (SAG) neurite outgrowth (Weber et al., 2017). Synergizing with MIF, another neurotrophic cytokine, the monocyte

Stress and cytokines in zebrafish

Being the core focus of psychoneuroimmunology, the immune, neural and endocrine systems interact and overlap (Chryssikopoulos, 1997; Yada and Nakanishi, 2002). In humans, the stress response and stress-induced psychiatric disorders (e.g., anxiety and depression) integrate neuroendocrine and immune mechanisms (Engelsma et al., 2002). In zebrafish, stressors may compromise the overall health status, increasing zebrafish susceptibility to pathogens and reducing their resistance. The two major

Zebrafish models relevant to studying microbiota-brain interplay

The human body hosts an enormous number of microbes performing multiple essential physiological functions (Goyal et al., 2015; Rogers et al., 2016). An imbalance of microbiota is strongly linked to Crohn's disease and ulcerative colitis (the two major forms of inflammatory bowel disease, IBD), irritable bowel syndrome (IBS), diabetes, metabolic syndrome and fatty liver disease (Biedermann and Rogler, 2015). Such patients often have comorbid psychiatric disorders, some of which (e.g., anxiety or

Conclusion

In summary, there are multiple human brain disorders which involve neuro-immune mechanisms, and whose translational modeling has been attempted in different organisms (Fig. 1, Fig. 2) (Dantzer, 2017; Karl et al., 1993; Kemeny and Gruenewald, 1999; Schubert and Schüssler, 2009). Immunopsychiatry – the rapidly developing field that studies these disorders – integrates neural (e.g., behavioral changes), immune (e.g., inflammation) and endocrine systems (e.g., cortisol stress response) at multiple

Declaration of interests

None.

Acknowledgement

The research was supported by the Russian Foundation for Basic Research (RFBR) grant 16-04-00851 to АVK. The authors thank Dr. S. Cheresiz for helpful discussion of zebrafish immune mechanisms, and D. Meshalkina for her help with this manuscript.

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