The Use of Zebrafish as a Non-traditional Model Organism in Translational Pain Research: The Knowns and the Unknowns

The ability of the nervous system to detect a wide range of noxious stimuli is crucial to avoid life-threatening injury and to trigger protective behavioral and physiological responses. Pain represents a complex phenomenon, including nociception associated with cognitive and emotional processing. Animal experimental models have been developed to understand the mechanisms involved in pain response, as well as to discover novel pharmacological and non-pharmacological anti-pain therapies. Due to the genetic tractability, similar physiology, low cost, and rich behavioral repertoire, the zebrafish (Danio rerio) is a powerful aquatic model for modeling pain responses. Here, we summarize the molecular machinery of zebrafish responses to painful stimuli, as well as emphasize how zebrafish-based pain models have been successfully used to understand specific molecular, physiological, and behavioral changes following different algogens and/or noxious stimuli (e.g., acetic acid, formalin, histamine, Complete Freund's Adjuvant, cinnamaldehyde, allyl isothiocyanate, and fin clipping). We also discuss recent advances in zebrafish-based studies and outline the potential advantages and limitations of the existing models to examine the mechanisms underlying pain responses from evolutionary and translational perspectives. Finally, we outline how zebrafish models can represent emergent tools to explore pain behaviors and pain-related mood disorders, as well as to facilitate analgesic therapy screening in translational pain research. © 2022 Bentham Science Publishers.International Zebrafish Neuroscience Research Con sortiumPROEX, (23038.005450/2020-19)Sirius UniversityZNRCCoordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPESConselho Nacional de Desenvolvimento Científico e Tecnológico, CNPqFundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, FAPERGS, (19/2551-0001764-2)Russian Science Foundation, RSF, (20-65-46006)National Centre for the Replacement Refinement and Reduction of Animals in Research, NC3RsFunding text 1: F.V.C., V.A.Q., and L.C.R. received CAPES fellowship. D.B.R. and A.R.S. are recipients of CNPq research productivity grant. D.B.R. research is also supported by PROEX/CAPES (process number 23038.005450/2020-19) and Programa PQ-Gaúcho FAPERGS (process number 19/2551-0001764-2) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Con-Funding text 2: F.V.C., V.A.Q., and L.C.R. received CAPES fellowship. D.B.R. and A.R.S. are recipients of CNPq research productivity grant. D.B.R. research is also supported by PROEX/CAPES (process number 23038.005450/2020-19) and Programa PQ-Ga?cho FAPERGS (process number 19/2551-0001764-2) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Con sortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 20-65-46006. L.U.S. is convenor of the FELASA working group producing a report on Pain Management in Zebrafish and is a member of the NC3Rs (UK) expert panel on zebrafish welfare. The funders did not influence writing and submission of this manuscript.Funding text 3: sortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 20-65-46006. L.U.S. is convenor of the FELASA working group producing a report on Pain Management in Zebrafish and is a member of the NC3Rs (UK) expert panel on zebrafish welfare. The funders did not influence writing and submission of this manuscript.Funding text 4: The authors thank the financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Finance Code 001, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). AVK collaboration is supported by Sirius University, Sochi, Russia

Exploring CNS Effects of American Traditional Medicines using Zebrafish Models

Although American traditional medicine (ATM) has been practiced for millennia, its complex multi-target mechanisms of therapeutic action remain poorly understood. Animal models are widely used to elucidate the therapeutic effects of various ATMs, including their modulation of brain and behavior. Complementing rodent models, the zebrafish (Danio rerio) is a promising novel organism in translational neuroscience and neuropharmacology research. Here, we emphasize the growing value of zebrafish for testing neurotropic effects of ATMs and outline future directions of research in this field. We also demonstrate the developing utility of zebrafish as complementary models for probing CNS mechanisms of ATM action and their potential to treat brain disorders. © 2022 Bentham Science Publishers.Applied Genetics MIPT, (075-15-2021-684)International Zebrafish Neurosci-ence Research ConsortiumSirius UniversitySouthwest University Zebrafish Platform Construction Funds (Chongqing, ChinaZNRCConselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, (305051/2018-0)Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, FAPERGS, (19/2551-0001-669-7, 19/2551-0001764-2)Russian Science Foundation, RSF, (20-65-46006)The study is supported by the Southwest University Zebrafish Platform Construction Funds (Chongqing, China). AVK is the Chair of the International Zebrafish Neurosci-ence Research Consortium (ZNRC) that coordinated this collaborative project. DBR receives the CNPq research productivity grant (process 305051/2018-0) and the FAPERGS “Gaucho” Researcher Program – PQG fellowship grant (process 19/2551-0001764-2). ACVVG is supported by the FAPERGS research fellowships 19/2551-0001-669-7. The study is partly supported by Sirius University (Sochi, Russia). Research collaboration here is supported by the Russian Science Foundation (RSF) grant 20-65-46006 to Prof. T.G. Amstislavskaya. The funders had no role in the design, analyses, and interpretation of the submitted study or the decision to publish. The study used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684)

Housing Conditions Differentially Affect Physiological and Behavioural Stress Responses of Zebrafish, as well as the Response to Anxiolytics

Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of group and individually housed fish, and found that individually housed individuals have lower basal cortisol levels. In our second experiment we found ethanol appeared to have an anxiolytic effect with individually housed fish but not those that were group housed. In our final experiment, we examined the effects of changing the fishes' water prior to tank diving as an additional acclimation procedure. We found that this had no effect on individually housed fish, but appeared to affect the typical tank diving responses of the group housed individuals. In conclusion, we demonstrate that housing represents an important factor in obtaining reliable data from this methodology, and should be considered by researchers interested in comparative models of anxiety in zebrafish in order to refine their approach and to increase the power in their experiments

Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests

Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs. © 2017, Mary Ann Liebert, Inc.The study was coordinated through the International Zebrafish Neuroscience Research Consortium (ZNRC), and this collaboration was supported by St. Petersburg State University Intramural Research program (DMM, EVK, AVK), Ural Federal University (AVK), Guangdong Ocean University (CS, AVK), the University of Passo Fundo (LJGB), CNPq grant 470260/2013 (LJGB) and CNPq research fellowships 301992/2014-2 (LJGB) and 307595/2015-3 (DBR). The funders had no involvement in the study design, data collection or analysis, and manuscript preparation. AVK is the Chair of ZNRC, and his research is supported by the Russian Foundation for Basic Research (RFBR) grant 16-04-00851. The authors thank Mr Rodrigo Zanandrea (University of Passo Fundo, Brazil) for his assistance with zebrafish cortisol analyses

Low‐carbon transition risks for finance

The transition to a low‐carbon economy will entail a large‐scale structural change. Some industries will have to expand their relative economic weight, while other industries, especially those directly linked to fossil fuel production and consumption, will have to decline. Such a systemic shift may have major repercussions on the stability of financial systems, via abrupt asset revaluations, defaults on debt, and the creation of bubbles in rising industries. Studies on previous industrial transitions have shed light on the financial transition risks originating from rapidly rising “sunrise” industries. In contrast, a similar conceptual understanding of risks from declining “sunset” industries is currently lacking. We substantiate this claim with a critical review of the conceptual and historical literature, which also shows that most literature either examines structural change in the real economy, or risks to financial stability, but rarely both together. We contribute to filling this research gap by developing a consistent theoretical framework of the drivers, transmission channels, and impacts of the phase‐out of carbon‐intensive industries on the financial system and on the feedback from the financial system into the rest of the economy. We also review the state of play of policy aiming to protect the financial system from transition risks and spell out research implications

Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009), which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaCentro Assistencial Cruz de MaltaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de MedicinaUNIFESP, Depto. de PediatriaSciEL