Psychoneuroimmunology and immunopsychiatry of zebrafish
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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