Zebrafish models of impulsivity and impulse control disorders.

Impulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional-defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD-specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.

The impact of housing environment color on zebrafish anxiety-like behavioral and physiological (cortisol) responses.

Color of the environment is an important factor modulating human and animal behavior and physiology. Animal models are a valuable tool to understand how colors affect social, cognitive and affective responses. The zebrafish (Danio rerio) is rapidly emerging as an important organism in neuroscience and physiology. Here, we examine whether the color of housing environment influences zebrafish anxiety-like behavior and whole-body cortisol levels. Overall, housing for 15 days in transparent and white holding tanks increases, and in black or blue tanks decreases, baseline anxiety-like behavior in adult zebrafish. Housing in blue tanks (vs. white) also reduced their whole-body cortisol levels. Taken together, our data suggest that color of the housing environment affects neurobehavioral and endocrine responses in zebrafish, with multiple implications for behavioral phenomics and animal welfare. Our study also reinforces zebrafish as a promising model organism to study neurobiology of compex brain-environment interactions.

Understanding sex differences in zebrafish pain- and fear-related behaviors.

Sex is an important variable in translational biomedical research. While overt sex differences have been reported for pain and fear-like behaviors in humans and rodents, these differences in other popular model organisms, such as zebrafish, remain poorly understood. Here, we evaluate potential sex differences in zebrafish behavioral responses to pain (intraperitoneal administration of 5% acetic acid) and fear stimuli (exposure to alarm substance). Overall, both male and female zebrafish exposed to pain (acetic acid injection) show lesser distance traveled, fewer top entries and more writhing-like pain-related behavior vs. controls, whereas female fish more robustly (than males) altered some other pain-like behaviors (e.g., increasing freezing episodes and time in top) in this model. In contrast, zebrafish of both sexes responded equally strongly to fear evoked by acute alarm substance exposure. Collectively, these findings emphasize the growing importance of studying sex differences in zebrafish behavioral and pain models.

Leishmania chagasi: effect of the iron deficiency on the infection in BALB/c mice.

Iron deficiency and visceral leishmaniasis are serious problems of public health. The aim of this study was to evaluate the effect of iron deficiency, induced by the iron chelator desferrioxamine, on the course of the infection by Leishmania chagasi in BALB/c mice. Our data show that the iron chelator caused significant reduction in hemoglobin concentration of treated mice and reduction in parasite load in spleen and liver. Significant differences were not observed in the production of IFN-gamma and IL-4 among the experimental groups. In conclusion, the data reported in this paper suggest that iron deficiency may favor the host. If there is not enough iron available to the parasite, its multiplication may be reduced and infection attenuated.

Putative anxiolytic-like behavioral effects of acute paracetamol in adult zebrafish.

Typically triggered by stress, anxiety disorders are most common and widespread mental illnesses. The zebrafish (Danio rerio) is rapidly becoming an important aquatic model species in stress research and central nervous system (CNS) drug screening. Paracetamol is currently the most prescribed medication for pain and fever, and is among the most used drugs globally. However, its CNS effects, especially on anxiety, in both clinical and animal studies remain poorly understood. Capitalizing on zebrafish as a powerful model system, here we evaluate the effects of paracetamol on anxiety-like behavior in adult fish, and its changes following an acute stress exposure. Overall, we report an anxiolytic-like profile of acute paracetamol treatment, and its alleviation of stress-evoked anxiety, in adult short-fin wild type zebrafish. Collectively, these findings suggest complex neuroactive effects of paracetamol, and reinforce the growing importance of zebrafish models for drug screening, including the search for novel putative anti-stress therapies.

Sex differences shape zebrafish performance in a battery of anxiety tests and in response to acute scopolamine treatment.

Sex differences influence human and animal behavioral and pharmacological responses. The zebrafish (Danio rerio) is a powerful, popular model system in neuroscience and drug screening. However, the impact of zebrafish sex differences on their behavior and drug responses remains poorly understood. Here, we evaluate baseline anxiety-like behavior in adult male and female zebrafish, and its changes following an acute 30-min exposure to 800-µM scopolamine, a common psychoactive anticholinergic drug. Overall, we report high baseline anxiety-like behavior and more individual variability in locomotion in female zebrafish, as well as distinct, sex-specific (anxiolytic-like in females and anxiogenic-like in males) effects of scopolamine. Collectively, these findings reinforce the growing importance of zebrafish models for studying how both individual and sex differences shape behavioral and pharmacological responses.

Color as an important biological variable in zebrafish models: Implications for translational neurobehavioral research.

Color is an important environmental factor that in multiple ways affects human and animal behavior and physiology. Widely used in neuroscience research, various experimental (animal) models may help improve our understanding of how different colors impact brain and behavioral processes. Complementing laboratory rodents, the zebrafish (Danio rerio) is rapidly emerging as an important novel model species to explore complex neurobehavioral processes. The growing utility of zebrafish in biomedicine makes it timely to consider the role of colors in their behavioral and physiological responses. Here, we summarize mounting evidence implicating colors as a critical variable in zebrafish models and neurobehavioral traits, with a particular relevance to CNS disease modeling, genetic and pharmacological modulation, as well as environmental enrichment and animal welfare. We also discuss the growing value of zebrafish models to study color neurobiology and color-related neurobehavioral phenomics, and outline future directions of research in this field.

Evaluation of the efficacy of probiotic VSL#3 and synbiotic VSL#3 and yacon-based product in reducing oxidative stress and intestinal permeability in mice induced to colorectal carcinogenesis.

The objective of the present study was to evaluate the effect of probiotic VSL#3 isolated or associated with a yacon-based product (synbiotic) on oxidative stress modulation and intestinal permeability in an experimental model of colorectal carcinogenesis. Forty-five C57BL/6J mice were divided into three groups: control (standard diet AIN-93 M); probiotic (standard diet AIN-93 M and multispecies probiotic VSL#3, 2.25 × 109 CFU), and synbiotic (standard diet AIN-93 M with yacon-based product, 6% fructooligosaccharides and inulin, and probiotic VSL#3, 2.25 × 109 CFU). The experimental diets were provided for 13 weeks. The probiotic and the yacon-based product showed antioxidant activity, with the percentage of DPPH radical scavenging equal to 69.7 ± 0.4% and 74.3 ± 0.1%, respectively. These findings contributed to reduce hepatic oxidative stress: the control group showed higher concentration of malondialdehyde (1.8-fold, p = 0.007 and 1.5-fold, p = 0.035) and carbonylated protein (2-fold, p = 0.008 and 5.6-fold, p = 0.000) compared to the probiotic and synbiotic groups, respectively. Catalase enzyme activity increased 1.43-fold (p = 0.014) in synbiotic group. The crypt depth increased 1.2-fold and 1.4-fold with the use of probiotic and synbiotic, respectively, compared to the control diet (p = 0.000). These findings corroborate the reduction in intestinal permeability in the probiotic and synbiotic groups, as measured by the percentage of urinary lactulose excretion (CON: 0.93 ± 0.62% × PRO: 0.44 ± 0.05%, p = 0.048; and CON: 0.93 ± 0.62% × SYN: 0.41 ± 0.12%, p = 0.043). In conclusion, the probiotic and synbiotic showed antioxidant activity, which contributed to the reduction of oxidative stress markers. In addition, they protected the mucosa from damage caused by chemical carcinogen and reduced intestinal permeability. PRACTICAL APPLICATION: The relationship between intestinal health and the occurrence of various organic disorders has been demonstrated in many studies. The use of probiotics and prebiotics is currently one of the main targets for modulation of intestinal health. We demonstrated that the use of a commercial mix of probiotic bacteria (VSL#3) isolated or associated with a yacon-based prebiotic, rich in fructooligosaccharides and inulin, is able to reduce the oxidative stress and intestinal permeability in a colorectal carcinogenesis model. These compounds have great potential to be used as a food supplement, or as ingredients in the development of food products.

Pro-social and anxiolytic-like behavior following a single 24-h exposure to 17ß-estradiol in adult male zebrafish.

Estradiol (17ß-estradiol, E2) is a crucial estrogen hormone that regulates sexual, cognitive, social and affective behaviors in various species. However, complex central nervous system (CNS) effects of E2, including its activity in males, remain poorly understood. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model system in translational neuroscience research. Here, we evaluate the effects of a single 24-h exposure to 20 µg/L of E2 on behavioral and endocrine (cortisol) responses in adult male zebrafish. Overall, E2 exerted pro-social effect in the social preference test, reduced whole-body cortisol levels, elevated exploration in the novel tank test and increased the shoal size in the shoaling test, indicative of an anxiolytic-like profile of this hormone in male zebrafish. Supporting mounting human and rodent evidence on the role of E2 in behavioral regulation, the observed pro-social and anxiolytic-like effects of E2 in male zebrafish reinforce the use of this aquatic organism in studying steroid-mediated CNS mechanisms of complex affective and social behaviors.

Sex differences in adult zebrafish anxiolytic-like responses to diazepam and melatonin.

Sex differences are an important variable in biomedical research. The zebrafish (Danio rerio) is rapidly becoming a critical novel model organism in translational neuroscience and neuropharmacology. Here, we examine the effects of sex on locomotor activity and anxiety-like behavior in adult zebrafish tested in the novel tank test following their exposure to two clinically relevant, common anxiolytic drugs diazepam and melatonin. While control female zebrafish were more active and anxious than males, both sexes showed anxiolytic responses to melatonin (0.232 mg/L) but only males responded to diazepam (16 µg/L). Revealing sex specificity in pharmacological responses, this study emphasizes the importance of sex differences in behavioral and pharmacological analyses in zebrafish. This may also be potentially relevant to modeling sex differences in clinical responses to anxiolytic drugs. Collectively, our data support sex differences in zebrafish behavioral responses and reinforce the growing utility of this aquatic model in CNS drug screening.

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish.

BACKGROUND: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening. AIM: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish. METHODS: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels. RESULTS: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses. CONCLUSION: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

Melatonin treatment reverses cognitive and endocrine deficits evoked by a 24-h light exposure in adult zebrafish.

Melatonin is an important pineal hormone that regulates human and animal circadian rhythms and sleep. Mounting clinical and rodent evidence indicates that melatonin also modulates affective behaviors and cognition. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in translational neuroscience research. Here, we evaluate the effects of a 24-h melatonin treatment on behavior and physiology of adult zebrafish with circadian rhythm disturbed by a 24-h light exposure. While such light exposure evoked overt cognitive and neuroendocrine (cortisol) deficits in zebrafish, these effects were reversed by a 24-h melatonin treatment. Collectively, these findings suggest a positive modulation of affective and cognitive phenotypes in zebrafish by melatonin, and reinforce the growing utility of zebrafish models for studying circadian, cognitive and behavioral processes and their neuroendocrine regulation in vivo.

A puericultura e os desafios decorrentes da pandemia de COVID-19

Com este estudo buscou-se analisar pela perspectiva médica, a evasão nas consultas de puericultura durante a pandemia de COVID-19. Trata-se de uma pesquisa qualitativa e descritiva, que foi realizada com cinco médicos atuantes nas Estratégias de Saúde da Família localizadas na cidade de Blumenau, do Médio Vale do Itajaí, em Santa Catarina. A coleta de dados foi realizada nos meses de julho e agosto de 2022, por meio de entrevista (gravada e transcrita), utilizando um questionário semiestruturado, por meio do método bola de neve, sendo escolhida a análise temática para análise dos dados. A pesquisa foi aprovada sob nº CAAE 58302622.0.0000.5370. A pandemia de COVID-19 impactou negativamente no acompanhamento das consultas de puericultura e as principais repercussões relacionam-se à diminuição das consultas; atraso no acompanhamento do desenvolvimento neuropsicomotor; aumento dos casos respiratórios com o retorno das crianças às creches e baixos índices de cobertura vacinal. Além disso, aspectos nutricionais foram evidenciados, como desmame precoce e mudanças dos hábitos alimentares (com aumento ou perda ponderal). Até o momento, as implicações acerca da COVID-19 na puericultura se tornaram inestimáveis, desta forma, os dados do estudo trazem dados relevantes para o planejamento de estratégias de fortalecimento das ações de puericultura, de promoção da saúde e prevenção de doenças.

Efeito da farinha de yacon (Smallanthus sonchifolius) na resposta imunológica intestinal no câncer colorretal / Effect of yacon meal (Smallanthus sonchifolius) on the intestinal immune response in colorectal cancer

Introdução: O câncer colorretal (CC) pode induzir graves complicações clínicas aos portadores dessa neoplasia. A farinha de yacon (FY) (Smallanthus sonchifolius) é rica em fruto-oligossacarídeos (FOS), que são fermentados por bifidobactérias, produzindo efeitos benéficos à saúde intestinal. Seu efeito no CC, entretanto, é ainda desconhecido, sendo o objetivo deste trabalho investigar os efeitos da FY sobre a resposta imunológica de mucosa em animais com CC induzido. Método: Ratos machos Wistar (n=44) foram divididos em grupo S (sem CC e sem FY na dieta), grupo C (com CC e sem FY na dieta), grupo Y (sem CC e com FY na dieta) e grupo CY (com CC e FY na dieta). Durante cinco semanas, os grupos C e CY receberam injeções de 1,2-Dimetilhidrazina para o desenvolvimento do CC, seguidas por duas semanas para formação das lesões neoplá- sicas. Após esse período, os grupos Y e CY consumiram dieta com FY em quantidades suficientes para fornecer 7,5% de FOS por duas semanas e os demais grupos consumiram dieta AIN-93M. Resposta imunológica da mucosa intestinal foi determinada pela dosagem de imunoglobulina A secretória (sIgA) nas fezes pelo método de ELISA. Dados foram avaliados por ANOVA e teste t pareado (p<0,05). Resultados: Após suplementação com FY na dieta, os níveis de sIgA no grupo CY foram superiores aos do grupo S. No grupo CY, os níveis de sIgA aumentaram quando comparados o início e final da intervenção. Conclusão: A FY foi capaz de aumentar os níveis da IgA fecal nos animais com CC.(AU)

Introduction: Colorectal cancer (CC) can induce serious clinical complications in patients with this neoplasm. Yacon flour (YF) (Smallanthus sonchifolius) is rich in fructooligosaccharides (FOS) that are fermented by bifidobacteria producing beneficial effects on intestinal health. Its effect on CC, however, is still unknown, and the objective of this work is to investigate the effects of YF on the immune response of mucosa in animals with induced CC. Methods: Male Wistar rats (n=44) were divided into group S (without CC and without YF in the diet), group C (with CC and without YF in the diet), group Y (without CC and with YF in the diet) And CY group (with CC and YF in the diet). For five weeks, groups C and CY received injections of 1,2-Dimethylhydrazine for the development of CC, followed by two weeks for the formation of neoplastic lesions. After this period, groups Y and CY consumed diet with YF in amounts sufficient to provide 7.5% of FOS for two weeks and the other groups, consumed diet AIN-93M. Immune response of intestinal mucosa was determined by secretory immunoglobulin A (sIgA) dosing in feces by the ELISA method. Data were evaluated by ANOVA and paired t-test (p<0.05). Results: After supplementation with YF in the diet, sIgA levels in the CY group were higher than those in the S group. In the CY group, sIgA levels increased when compared to the beginning and end of the intervention. Conclusion: FY was able to increase faecal IgA levels in animals with CC.(AU)