Zebrafish models for attention deficit hyperactivity disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is a common, debilitating neurodevelopmental disorder associated with inattentiveness, pathological hyperactivity and impulsivity. Despite the mounting human and animal evidence, the neurological pathways underlying ADHD remain poorly understood. Novel translational model organisms, such as the zebrafish (Danio rerio), are becoming important tools to investigate genetic and pathophysiological mechanisms of various neuropsychiatric disorders. Here, we discuss ADHD etiology, existing animal models and their limitations, and emphasize the advantages of using zebrafish to model ADHD. Overall, the growing utility of zebrafish models may improve our understanding of ADHD and facilitate drug discovery to prevent or treat this disorder. © 2019 Elsevier Lt

Naloxone Prolongs Abdominal Constriction Writhing-Like Behavior in a Zebrafish-Based Pain Model

The ability to detect noxious stimuli is essential to survival. However, pathological pain is maladaptive and severely debilitating. Endogenous and exogenous opioids modulate pain responses via opioid receptors, reducing pain sensibility. Due to the high genetic and physiological similarities to rodents and humans, the zebrafish is a valuable tool to assess pain responses and the underlying mechanisms involved in nociception. Although morphine attenuates pain-like responses of zebrafish, there are no data showing if the antagonism of opioid receptors prolongs pain duration in the absence of an exogenous opioid. Here, we investigated whether a common opioid antagonist naloxone affects the abdominal constriction writhing-like response, recently characterized as a zebrafish-based pain behavior. Animals were injected intraperitoneally with acetic acid (5.0%), naloxone (1.25 mg/kg; 2.5 mg/kg; 5.0 mg/kg) or acetic acid with naloxone to investigate the changes in their body curvature for 1 h. Acetic acid elicited a robust pain-like response in zebrafish, as assessed by aberrant abdominal body curvature, while no effects were observed following PBS injection. Although naloxone alone did not alter the frequency and duration of this behavior, it dose-dependently prolonged acetic acid-induced abdominal curvature response. Besides reinforcing the use of the abdominal writhing-like phenotype as a behavioral endpoint to measure acute pain responses in zebrafish models, our novel data suggest a putative role of endogenous opioids in modulating the recovery from pain stimulation in zebrafish. © 2019 Elsevier B.V.We recognize the financial support and fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) . F.V.C. was recipient of CAPES fellowship. J.C. and F.V.S. receive the CNPq fellowship. D.B.R. is a recipient of CNPq research productivity grant ( 305051/2018-0 ) and his work is also supported by the PROEX/CAPES (process number 23038.005848/2018-31) and PRONEM/FAPERGS (process number 16/2551-0000248-7) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 19-15-00053. All authors contributed to the preparation of the manuscript and approved its final version. The funders had no influence on the study design, collection, analysis, and interpretation of data, as well as on writing and submission of this manuscript

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

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