Time to (finally) acknowledge that fish have emotionality and pain

The increasing work using fish as a model organism calls for a better understanding of their sentience. While growing evidence suggests that pain and emotionality exist in zebrafish, many deniers continue to ignore the evidence. Here we revisit the main conceptual breakthroughs in the field that argue clearly for pain and emotionality. We call for an end to denial and a focus on studying the mechanisms of fish pain and emotionality, and their translational relevance to human conditions

Developing translational biological psychiatry: Learning from history to build the future

Psychiatric disorders are among the most complex human disorders that, albeit often difficult to diagnose and treat, are widespread in modern society. Biological psychiatry studies biological functions of the central nervous system as mental disorders develop. Today’s biological psychiatry is facing multiple conceptual problems that prevent our deeper understanding of disease pathogenesis and delay the invention of new treatments. Thus, providing a historical context to this rapidly developing field may help scientists better understand the existing challenges and their potential solutions. Here, we discuss the main conceptual problems and paradigms of biological psychiatry, including the lack of reproducibility and/or valid theories, through an historical overview of its role in addressing theoretical and clinical questions. We propose a wider use of the translational approach in psychiatry to expand our analyses of psychiatric disorders to other species, and as a tool to create and further develop theories and concepts in this field.This work was supported by the Russian Foundation for Basic Research (RFBR) Grant 16-04-00851

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders

Abnormal repetitive behaviors (ARBs) are a prominent symptom of numerous human brain disorders and are commonly seen in rodent models as well. While rodent studies of ARBs continue to dominate the field, mounting evidence suggests that zebrafish (Danio rerio) also display ARB-like phenotypes and may therefore be a novel model organism for ARB research. In addition to clear practical research advantages as a model species, zebrafish share high genetic and physiological homology to humans and rodents, including multiple ARB-related genes and robust behaviors relevant to ARB. Here, we discuss a wide spectrum of stereotypic repetitive behaviors in zebrafish, data on their genetic and pharmacological modulation, and the overall translational relevance of fish ARBs to modeling human brain disorders. Overall, the zebrafish is rapidly emerging as a new promising model to study ARBs and their underlying mechanisms. © 2019 Elsevier B.V

Zebrafish as a Model of Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) caused by aberrant brain growth and development are life-long, debilitating illnesses that markedly impair the quality of life. Animal models are a valuable tool for studying NDD pathobiology and therapies. Mounting evidence suggests the zebrafish (Danio rerio) as a useful model organism to study NDDs, possessing both high physiological homology to humans and sensitivity to pharmacological and genetic manipulations. Here, we summarize experimental models of NDDs in zebrafish and highlight the growing translational significance of zebrafish NDD-related phenotypes. We also emphasize the need in further development of zebrafish models of NDDs to improve our understanding of their pathogenesis and therapeutic treatments. © 2019 IBROThis research is supported by the Russian Science Foundation grant 19-05-00053. KAD is supported by the Russian Foundation for Basic Research grant 18‐34‐00996, the President of Russia PhD Fellowship and the SPSU Rector's Productivity Fellowship for PhD students. ACVVG is supported by the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) research fellowships 17/2551-0001-269-0. AVK is the President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior .com) and the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) that coordinated this multi-laboratory collaborative project

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy. © 2020, The Author(s).The research was supported by the Russian Science Foundation (RSF) Grant 19‐15‐00053. KAD is supported by the President of Russia Graduate Fellowship, the Special Rector’s Productivity Fellowship for SPSU PhD Students, and the Russian Foundation for Basic Research (RFBR) grant 18‐34‐00996. ADP was supported by St. Petersburg University (project ID 51555422). The research team was supported by St. Petersburg State University state budgetary funds (project ID 51130521). AVK is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) and President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com) that coordinated this collaborative multi-laboratory project. The consortium provided a collaborative idea exchange platform for this study. It is not considered as an affiliation, and did not fund the study. AVK is supported by the Southwest University Zebrafish Platform Construction Fund. TGA’s research is supported by the budgetary funding for basic research from the Scientific Research Institute of Physiology and Basic Medicine (AAAA-A16-116021010228-0, Novosibirsk, Russia). This study utilized equipment of the Core Facilities Centre “Centre for Molecular and Cell Technologies” of St. Petersburg State University. The funders had no role in the design, analyses, and interpretation of the submitted study, or decision to publish

Cross-species Analyses of Intra-species Behavioral Differences in Mammals and Fish

Multiple species display robust behavioral variance among individuals due to different genetic, genomic, epigenetic, neuroplasticity and environmental factors. Behavioral individuality has been extensively studied in various animal models, including rodents and other mammals. Fish, such as zebrafish (Danio rerio), have recently emerged as powerful aquatic model organisms with overt individual differences in behavioral, nociceptive and other CNS traits. Here, we evaluate individual behavioral differences in mammals and fish, emphasizing the importance of cross-species analyses of intraspecies variance in experimental models of normal and pathological CNS functions. © 2019 IBROAVK laboratory is supported by the Southwest University (Chongqing, China) Zebrafish Platform construction funds. This research is supported by the Russian Science Foundation grant 19-15-00053 . KAD is supported by the Russian Foundation for Basic Research ( RFBR) grant 18-34-00996 , Fellowship of the President of Russia and Special Rector’s Fellowship for SPSU PhD Students. DBR receives the CNPq research productivity grant (305051/2018-0), and his work is also supported by the PROEX/CAPES fellowhip grant 23038.004173/2019-93 (Brazil). MP receives funding from the British Academy (UK) . BDF is supported by a CAPES Foundation studentship (Brazil). FC is supported by the Father’s Foundation and the Fast Data Sharing-2036 programs. AVK is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) Special 2018-2019 Task Force that coordinated this multi-laboratory collaborative project

Time to (finally) acknowledge that fish have emotionality and pain

The increasing work using fish as a model organism calls for a better understanding of their sentience. While growing evidence suggests that pain and emotionality exist in zebrafish, many deniers continue to ignore the evidence. Here we revisit the main conceptual breakthroughs in the field that argue clearly for pain and emotionality. We call for an end to denial and a focus on studying the mechanisms of fish pain and emotionality, and their translational relevance to human conditions