The zebrafish (Danio rerio) is a small freshwater teleost fish species that is increasingly utilized in biomedical research, particularly in neuroscience and biological psychiatry. Currently, zebrafish is the second-most utilized model organism in biomedicine globally, after mice, based on the number of animals tested each year. The model’s significance results from its experimental ease of use, affordability, conservation of fish physiology, relatively high genetic homology with humans (70%), rapid development, and potential for high-throughput bioscreening of drugs and genetic mutations. Over the past 15 years, our laboratory has conducted extensive experimental work to establish the principles behind using zebrafish to study various brain pathologies, including acute and chronic stress, anxiety, and depression, as well as probing their molecular mechanisms. In addition, existing behavioral models to study the central nervous system (CNS) development and new data on the zebrafish’s critical role in memory research were reviewed. Furthermore, this study will illustrate the effectiveness of integrating zebrafish models with advanced biological research techniques, such as molecular biology, bioinformatics, omics technologies, and chemical biology methods. For example, adult zebrafish experiencing chronic stress exhibit behavioral affective syndromes along with changes in neurochemistry, specifically in the metabolism of serotonin and dopamine in the telencephalon. Moreover, alterations in the expression of genes regulating neurotransmitter receptors, glial biomarkers, cytoskeleton, and pro- and anti-inflammatory cytokines, occur in the brain. In particular, we will focus on neuroimmune and epigenetic mechanisms of CNS pathogenesis in zebrafish models, including changes in the expression of apoptotic genes in the brain. Additionally, our own findings on using artificial intelligence (AI) systems to study zebrafish behavior after administering various neurotropic drugs, such as anxiolytics, antidepressants, psychostimulants, and hallucinogens will be presented. In general, zebrafish is a strategic and promising model organism for translational neuroscience research, creating new models of CNS pathogenesis and finding new drugs to treat various human brain diseases. Studies of CNS pathogenesis in zebrafish are critical because of their evolutionary conservatism and ease of laboratory application, revealing novel brain disease biomarkers and potential remediation targets. Meanwhile, certain distinctive aspects of the biology and neurophysiology of zebrafish facilitate the resolution of supplementary experimental issues, thereby enhancing data and discoveries attained in typical animal models using rodents.
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