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Over the years, scientific research with fish models has grown at a rapid pace, and issues such as animal welfare are becoming increasingly important in various areas of animal husbandry and experimentation. Here, we evaluated whether Danio rerio behavior is affected by long-term maintenance (75 days) in an enriched environment or a chronic stress (CS) situation. In addition, we evaluated some biochemical parameters related to redox status. We concluded that long-term maintenance of zebrafish in enriched environment might induce an anxiety-like behavior pattern when these fish are faced with an acute subsequent stressor. These anxiety results, the increased school cohesion, and the absence of oxidative damage allow us to hypothesize that the fish maintained in environmental enrichment (EE) situation is more reactive, showing a strong protective reaction to the stress. From an applicable perspective, we show that both too much stress and too little stress are not ideal for zebrafish stocks. In CS situations, fish can habituate and might not respond optimally to test conditions. In opposite, the low stress promoted by environmental enrichment also renders the fish incapable of dealing with occasional stressors optimally, because now even normal conditions appear stressful to them and may elicit fear behaviors they normally would not exhibit.
Assuntos
Comportamento Animal , Biomarcadores , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Biomarcadores/metabolismo , Criação de Animais Domésticos/métodos , Ansiedade , Abrigo para Animais , Estresse Fisiológico , Masculino , Estresse Psicológico , Feminino , Bem-Estar do AnimalRESUMO
Numerous chemical compounds are found in aquatic environments; among them are pesticides. Pesticides are widely used worldwide, and this use has progressively increased in recent decades, resulting in the accumulation of potentially toxic compounds in surface waters. Dimethylamine-based herbicides (DBH) and imidacloprid-based insecticides (IBI) have low soil absorption and high water solubility, facilitating the arrival of these compounds in aquatic environments. In this study, our objective was to analyze whether two pesticides, DBH and IBI at environmentally relevant concentrations of 320 µg/L for each compound, and their mixtures impact the behavioral and endocrine parameters of adult zebrafish, verifying the effect of pesticides on exploratory behavior and social and analyzing hormonal parameters related to stress. Acute exposure to the mixture of pesticides reduced fish locomotion. Pesticides alone and in combination did not affect cortisol levels in exposed animals. Pesticides, when tested together, can cause different effects on non-target organisms, and the evaluation of mixtures of these compounds is extremely important.
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Locomoção , Neonicotinoides , Nitrocompostos , Praguicidas , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Neonicotinoides/toxicidade , Locomoção/efeitos dos fármacos , Praguicidas/toxicidade , Nitrocompostos/toxicidade , Dimetilaminas , Poluentes Químicos da Água/toxicidadeRESUMO
The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer's and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes-catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications.
Assuntos
Canabidiol , Cannabis , Animais , Cannabis/química , Alumínio , Antioxidantes , Acetilcolinesterase , Peixe-Zebra , Canabidiol/farmacologia , Óleos , Dronabinol/farmacologiaRESUMO
Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.
Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Peixe-Zebra , Macrófagos , PeptídeosRESUMO
The growing consumption of psychoactive drugs, such as Venlafaxine (VFX), can negatively affect the organisms. Our main hypothesis is to investigate if VFX at human-used doses could exert effects on the behavioral, nervous, and antioxidant systems of two different organisms, zebrafish and C. elegans. We evaluated the effect of acute exposure to VFX at four concentrations (0, 37.5, 75, and 150 mg L-1) using toxicological indicator assessments. We evaluated zebrafish behavior using the novel tank test (NTT), social preference test (SPT), cortisol levels, acetylcholinesterase (AChE) activity, and antioxidant system. In C. elegans, we evaluated body bends, defecation cycles, pharyngeal pumping, AChE activity, and antioxidant system. C. elegans do not show alterations in the behavior analysis of pharyngeal pumping and body bends. Instead, the defecation cycle was increased in the highest dose of VFX. AChE activity also does not have differences compared to the control, the same occurs in lipid peroxidation rates. These results showed that nematodes were more resistant to changes when exposed to VFX. Zebrafish exposed to VFX showed changes in the NTT and SPT test, mainly in the anxiolytic pattern, suggesting that VFX alters this anxiolytic-like behavior. Comparing both organisms, we can observe that zebrafish seems to be more sensitive in this neurotoxicological evaluation.
Assuntos
Ansiolíticos , Peixe-Zebra , Animais , Humanos , Cloridrato de Venlafaxina/toxicidade , Caenorhabditis elegans , Acetilcolinesterase , AntioxidantesRESUMO
The imidacloprid-based insecticides (IBIs) are among the most used insecticides worldwide, and chronic and acute toxic effects (days exposure protocols) have been reported in several species in studies of IBIs at lethal concentrations. However, there is little information on shorter time exposures and environmentally relevant concentrations. In this study, we investigated the effect of a 30-min exposure to environmentally relevant concentrations of IBI on the behavior, redox status, and cortisol levels of zebrafish. We showed that the IBI decreased fish locomotion and social and aggressive behaviors and induced an anxiolytic-like behavior. Furthermore, IBI increased cortisol levels and protein carbonylation and decreased nitric oxide levels. These changes were mostly observed at 0.013 and 0.0013 µg·L-1 of IBI. In an environmental context, these behavioral and physiological disbalances, which were immediately triggered by IBI, can impair the ability of fish to evade predators and, consequently, affect their survival.
Assuntos
Inseticidas , Poluentes Químicos da Água , Animais , Inseticidas/toxicidade , Inseticidas/metabolismo , Peixe-Zebra/fisiologia , Hidrocortisona , Neonicotinoides/toxicidade , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
The trade of aquarium organisms is growing worldwide. This market depends on a continuous supply of healthy and colorful aquatic animals, but this sector has few initiatives. However, in the last decade, there has been a growing interest in researching captive breeding of these animals, aiming to develop a more sustainable aquarium hobby. Larviculture is an important phase in the cultivation process because the larvae are more sensitive to stress and variations in the bulk of variables, such as temperature, salinity, nutritional management, light intensity and spectrum, and environmental background colors. Because background color could be a promoter variable of proper welfare, we tested whether it affects the endocrine response of tomato clownfish Amphiprion frenatus larvae to an acute stress challenge. We show that background color influences the endocrine stress axis responsiveness in tomato clownfish. When fish were subjected to a standard acute stressor of 61 days after hatching, only fish adapted to white walls increased the whole-body cortisol levels. From the results presented herein, we recommend that white tanks be avoided for A. frenatus larviculture. Both, the less stress level and the good welfare condition of larvae reared in colored tanks may have robust, practical applications since almost all clownfish in the ornamental aquarium trade come from captive breeding.
Assuntos
Perciformes , Solanum lycopersicum , Animais , Melhoramento Vegetal , Perciformes/fisiologia , Peixes , LarvaRESUMO
Good Laboratory Practice (GLP) is a management quality control system that encompasses the organizational process and conditions under which non-clinical health and environmental studies are carried out. According to the World Health Organization, GLP must contain five topics: resources, characterization, rules, results, and quality control. The aim of this work is to address a review according to WHO standard to the implementation of Good Laboratory Practices in zebrafish (Danio rerio) facility. Considering that the promotion of one health (animal, human, and environmental) associated with an education plan, protocols, and records are fundamental to guarantee the safety and integrity of employees, animals and the environment as well as reliability in the results generated. In a way, Brazil still needs improvements related to the wellfare of aquatic organisms (national laws, international agreements, corporate programs, and others); especially in relation to its use in research and technological development. In this way, the implementation of GLPs provide valuable guidance for improving animal welfare and worker safety, facilitating the standardization of research.
As Boas Práticas de Laboratório (BPL) são um sistema de controle de qualidade gerencial que abrange o processo organizacional e as condições sob as quais os estudos não clínicos de saúde e meio ambiente são desenvolvidos. Conforme a Organização Mundial da Saúde (OMS) as BPL devem conter cinco tópicos: recursos, caracterização, regras, resultados e controle de qualidade. O objetivo deste trabalho foi apresentar uma revisão conforme o padrão da OMS para a implementação das BPL em biotério de zebrafish. Considerando que a promoção da saúde única (animal, humana e ambiental) associada a um plano de educação, protocolos e registros são fundamentais para garantir a segurança e a integridade dos trabalhadores/pesquisadores, animais e meio ambiente assim como confiabilidade nos resultados gerados. De certa forma o Brasil ainda necessita de melhorias relacionadas ao bem-estar de organismos aquáticos (leis nacionais, acordos internacionais, programas corporativos e outros); especialmente em relação à utilização destes na pesquisa e desenvolvimento tecnológico. Desta forma, a implementação de BPL fornece uma orientação valiosa para a melhoria do bem-estar animal, e segurança do trabalhador vindo a facilitar a padronização da pesquisa.
Assuntos
Animais , Peixe-Zebra , Bem-Estar do Animal/legislação & jurisprudência , Experimentação Animal/legislação & jurisprudência , Animais de Laboratório , Padrões de Referência , BrasilRESUMO
The consumption of progestins has increased considerably in recent decades, as has their disposal into the environment. These substances can negatively affect the reproduction, physiology, and behavior of non-target organisms, such as fish. We aimed to evaluate the effects of exposure to environmentally relevant concentrations of levonorgestrel-control birth based (1.3, 13.3, 133, and 1330 ng/L) on the development and behavior of zebrafish (Danio rerio) in terms of mortality, hatching, spontaneous movement, and larval and adult behavioral tests. Exposure caused anxiogenic-like behavior in larvae, which persisted in adults, as demonstrated by the light-dark test. In contrast, it caused anxiolytic-like behavior in the novel tank test. There was a high mortality rate at all tested concentrations and increases in the hormone cortisol at 13.3 ng/L that affected the sex ratio. These changes may lead to an ecological imbalance, emphasizing the risk of early exposure to progestins in the environment.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Humanos , Animais , Feminino , Peixe-Zebra/fisiologia , Levanogestrel/toxicidade , Progestinas/toxicidade , Larva , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepção , Poluentes Químicos da Água/toxicidade , Embrião não MamíferoRESUMO
Highly toxic chemical compounds are present in rivers and lakes, endangering the survival of non-target species. To evaluate the effects of environmental contamination on non-target species, we used the zebrafish as an animal model. Environmental concentrations of the widely used pesticides, glyphosate (GBH) at 4.8 µg·L-1 and 2,4-dichlorophenoxyacetic acid (DBH) at 3.4 µg·L-1, were used. The animals were exposed during the entire period of organogenesis and evaluated in our previous study regarding initial developmental parameters. In the present study, we evaluate these fish when achieve the adult phase, using the novel tank test (NTT) and the aversivity test. In the second step, the animals were allowed to reproduce, and the initial parameters of development, behavioral parameters in the open field test (OFT) and in the aversivity test (AST), and biochemical biomarkers as acetylcholinesterase (AChE), catalase (CAT), and superoxide dismutase (SOD) in the F1 generation were studied. Fish exposed to GBH showed hypermobility, and their anti-predatory reaction was impaired during adulthood, indicating a persistent effect. We also showed that fish had impaired behavioral and survival changes in the F1 generation as well as effects on AChE activity and antioxidant enzymes, characterizing a transgenerational effect. The fish did not show persistent effects in adulthood due to DBH exposure; however, they were unable to reproduce. Our findings demonstrate the serious impact of pesticides on fish, where the effects of contamination can affect future generations and compromise the species' survival.
Assuntos
Resíduos de Praguicidas , Praguicidas , Poluentes Químicos da Água , Ácido 2,4-Diclorofenoxiacético , Acetilcolinesterase , Animais , Antioxidantes , Biomarcadores , Catalase , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Superóxido Dismutase , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-ZebraRESUMO
Ilex paraguariensis (Herb mate) is a native plant from South America, widely consumed through the infusion of dried leaves. The presence of antioxidant properties in herb mate may be relevant and contribute to evaluating the effect of its compounds against oxidative stress, which could cause neurodegenerative diseases. Despite having health benefits, there are reports of the presence of heavy metals in extracts obtained from the infusion. One of these metals is iron (Fe), found in large amounts in herb mate. To reverse the cumulative effects of metals and Fe in the body, the use of Deferoxamine (Dfx) is indicated, being a potent chelator of Fe. In this work, we aimed to evaluate the antioxidant potential of the micro-encapsulated extract of I. paraguariensis (MEIP) supplemented with Dfx on zebrafish behavior and biochemical biomarkers. To evaluate the effect per se and the supplementation, four groups were established: the first group was the control (water); the second, fish treated with MEIP; the third group was formed of fish treated with Dfx; while the fourth group was treated with both MEIP and Dfx. When applied alone, Dfx presents an anxiogenic-like pattern on zebrafish (Danio rerio), while the MEIP shows an anxiolytic-like behavior. The antioxidant enzymes are re-modulated close to control when the MEIP + Dfx is applied. The cholinergic system shows an activation of the signaling, as well as the heme radical group formation, which is not affected by the Dfx-chelating effect. Thus, the supplementation of MEIP with Dfx is important to transform this extract into one that is safer and healthier for human consumption.
RESUMO
The harmful effects of heavy metals on organisms have not been fully described. At present, there is a close relationship between neurodegenerative diseases and copper toxicity. In addition, the copper effect on the central nervous system is followed by high levels of free radicals in different body tissues. An increase in free radical levels leads to aging-related diseases, resulting in the appearance of senile comorbidities. An increase in the consumption of natural compounds that could help to reduce this dangerous effect on organisms was observed. Pitaya (Hylocereus undatus) is a tropical fruit with great antioxidant potential and can help the organism with oxidative damage. This study evaluated the effect of H. undatus on zebrafish organisms in front of copper-induced toxicity. Therefore, the behavior, cholinergic system, antioxidant enzymes, and ALAD activity were evaluated as biomarkers. Our results highlight the great potential of Pitaya's pulp to reduce the levels of anxiety and aggressivity in fish and reduce cortisol levels. It could mediate the normal response of the cholinergic nervous system, antioxidant enzymes, and ALAD activity. Therefore, our data suggest that pitaya might improve the senile aging. PRACTICAL APPLICATIONS: The potential practical application of this study is related to the neuroprotective effect of the Hylocereus undatus microencapsulated pulp extract against metal-induced impairments. The results have shown that this extract is able to reduce the copper-induced damage modulating the antioxidant system and the cholinergic nervous system. One of the implicated potentials of use for this extract is the food supplementation to its fortification.
Assuntos
Antioxidantes , Cactaceae , Animais , Antioxidantes/farmacologia , Colinérgicos , Cobre/toxicidade , Frutas , Extratos Vegetais/farmacologia , Peixe-Zebra/fisiologiaRESUMO
Pesticides reach water bodies through different routes, either owing to incorrect packaging disposal, direct application to control macrophytes, leaching from fields, or natural degradation processes. In the aquatic environment, adverse effects in non-target species that come in contact with these substances are poorly understood. Currently, the most used pesticides are glyphosate (GBH) and 2,4-dichlorophenoxyacetic acid-based herbicides (DBH), as its presence in water bodies is already known, we used environmental concentrations and our exposure time comprised the entire period of organogenesis (3-120 h post-fertilization). We evaluated the response of embryos in their early development with the parameters of mortality, hatching, spontaneous movement, and heart rate; and it's through behavior the open field test and aversive stimulus, as well as biochemical analyzes of acetylcholinesterase activity (AChE), catalase (CTL) and superoxide dismutase (SOD) as a possible mechanism of action. Exposure to GBH decreased survival, caused hypermobility and anxiolytic behavior, negatively affected the anti-predatory behavior of the larvae, and increases acetylcholinesterase activity, whereas exposure to DBH caused only slight hypermobility in the larvae and increases acetylcholinesterase activity. These changes may compromise the perpetuation of the species, the search for partners/food, and facilitate the action of predators, which can result in serious ecological consequences.
Assuntos
Herbicidas , Praguicidas , Poluentes Químicos da Água , Acetilcolinesterase/metabolismo , Animais , Herbicidas/toxicidade , Larva , Praguicidas/toxicidade , Água , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismoRESUMO
Copper (Cu) is an essential metal and it is important for metabolism. However, in high concentrations, it becomes toxic. Metal-induced toxicity is the cause of many neurodegenerative diseases. So it is necessary to search mechanisms to find ways of healthy aging. Natural compounds and diets based on fruits are increasingly common and could lead to a healthy life. Pitaya (Hylocereus undatus) is a tropical and Latin American, fruit that is gaining more popularity due to its antioxidant properties. Here, we evaluate the preventive and curative effect of different doses of microencapsulated pulp H. undatus extract on copper-induced toxicity. For this we use the nematode Caenorhabditis elegans, to investigate the effects of pitaya extract on behavior, lipid peroxidation, antioxidant chaperon, and cholinergic nervous system (ColNS). Results showed behavioral changes, decreased cell death biomarkers, and lipid peroxidation caused by copper, and these toxic effects were prevented and reverted by Pitaya's extract. After all, the extract can be used in diet as a supplement and studied to treat or prevent specific diseases, some of them linked to contamination and senility-related conditions. PRACTICAL APPLICATIONS: This research has been aimed to provide the uses of Hylocereus undatus microencapsulated pulp extract for the prevention and treatment of copper-induced toxicity. We have been shown that Pitaya is a good source of antioxidant compounds that can ameliorate the antioxidant system as well as the cholinergic nervous system avoiding behavior changes before and after the metal toxicity of copper. Therefore, the potential applications and common use of this extract can serve as food supplementation to prevent metal oxidative damage as well as to repair clinical cases of copper poisoning.
Assuntos
Cactaceae , Frutas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Caenorhabditis elegans , Colinérgicos/metabolismo , Cobre/toxicidade , Frutas/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologiaRESUMO
The addition of fruit to the diet is very important, and we can use nutraceutical and functional foods for this supplement. A little-known fruit is a red pitaya (Hylocereus undatus) that has been widely reported to have a high antioxidant potential. In this study, we analyzed the in vitro and in vivo antioxidant capacity of microencapsulated pitaya extract on the behavior, antioxidant, and nervous system of the nematode Caenorhabditis elegans. The worms were treated with fruit extract before and after juglone-induced stress, to determine the protective or curative effects of pitaya. We have been evaluated cholinergic, antioxidant, and behavioral biomarkers. We have evidenced that the pulp of pitaya contains antioxidant compounds and can serve as a potential nutraceutical product. In addition, the fruit extract was effective in preventing and/or reverse the stress-induced damages, even at high levels of chemical stress at all evaluated parameters. PRACTICAL APPLICATIONS: The potential applications and uses aimed by this research are related to the supplementation of foods given the antioxidant effect. Our data suggested that the effect of the pitaya fruit microencapsulated pulp extract was effective to prevent and repair the damage caused by oxidative stress. Besides the use of this microencapsulated extract can be an auxiliary in the treatment of diseases related to oxidative damage as well as promoting senescent aging. Another important use is the application of this extract as a dietary supplement to fortify the antioxidant system.
Assuntos
Antioxidantes , Cactaceae , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Cactaceae/química , Caenorhabditis elegans , Colinérgicos/análise , Frutas/química , Extratos Vegetais/químicaRESUMO
Genistein is a phytoestrogen, which is structurally similar to 17ß-estradiol. It is present in plants, food, and as a contaminant in effluents. In this article, we demonstrate the effects of embryonic exposure to three different concentrations of genistein (10 µg/L, 40 µg/L, and 80 µg/L) which is similar to those found in effluents. Zebrafish eggs were exposed during the first 72 h post-fertilization (hpf). Heart rate was evaluated at 48 hpf and mortality rate was assessed during the first 72 hpf. The light/dark (LDT) and open field (OFT) behavioral tests were applied to the larvae (6 dpf), and the novel tank (NTT), social preference (SPT), light-dark (LDT), and sexing tests were performed on adult fish (90 dpf). Embryonic exposure to genistein caused anxiolytic-like behavior in both larvae and adult animals. In adult stage, we observed an increase in locomotor activity and antisocial behavior in the concentration of 40 µg/L. There was an increase in the mortality rate in all concentrations when compared to the control and an increase in heart rate at the concentration of 80 µg/L. Exposure to 10 µg/L generated a higher frequency of females when compared to the control group. Our results show that exposure to genistein during the embryonic phase brings damage in the short and long term as it increases the mortality rate and leads to behavioral disorders both in the larval stage, with perpetuation until adult stage. The anxiolytic-like effect and less social interaction are effects that harm fish survival.
Assuntos
Genisteína , Peixe-Zebra , Animais , Transtorno da Personalidade Antissocial , Embrião não Mamífero , Feminino , Genisteína/toxicidadeRESUMO
The dopaminergic system of zebrafish is complex and the numerous pathways and receptors in the central nervous system (CNS) are being extensively studied. A critical factor for the synthesis, activation and release of catecholamines (CAs) is the presence of tyrosine hydroxylase, an enzyme which converts L-tyrosine into levodopa. Levodopa thus is the intermediary in the synthesis of dopamine (DA) and norepinephrine (NE) and promotes its release; therefore, CAs play an important role in the CNS with hormonal functions. Here, we use levodopa/carbidopa to clarify the involvement of the dopaminergic pathway in the stress response in zebrafish submitted to an acute stress challenge. Acute stress was induced by chasing fish with a net for 2 min and assessed by measuring whole-body cortisol levels. Two experiments were carried out, the first with exposure to levodopa/carbidopa and the second with exposure to AMPT and levodopa/carbidopa. Levodopa/carbidopa balances the stress response through its action on the zebrafish hypothalamic-pituitary-adrenal (HPA) axis. Changes in cortisol levels suggest that DA was related to the balance of the stress response and that NE decreased this response. These effects were specific to stress since levodopa/carbidopa did not induce changes in cortisol in non-stressed fish.
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Carbidopa/farmacologia , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Levodopa/farmacologia , Estresse Fisiológico , Peixe-Zebra/metabolismo , Glândulas Suprarrenais/metabolismo , Animais , Neurônios Dopaminérgicos/metabolismo , Combinação de Medicamentos , Inibidores Enzimáticos/farmacologia , Feminino , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/metabolismo , alfa-Metiltirosina/farmacologiaRESUMO
We report the effects of acute and chronic stress on the expression of selective immune-related genes and markers of neuronal function in the brain of the zebrafish (Danio rerio). Fish were distributed into three groups: the non-stressed control group; the acute stress (AS) group, submitted to a single stressing episode; and the unpredictable chronic stress (UCS) group, submitted to two daily stressing episodes of alternating times and types of stress. The stressing protocols were applied for a period of 14 days. The UCS protocol triggered the expression of the pro-inflammatory cytokine genes IL-1ß and TNF-α, the anti-inflammatory cytokine IL-10 (negative feedback from the immune system), reduction in cFOS gene expression, and caused neuro-inflammation. The AS protocol had no effect on gene expression. Altered expression of cytokine genes, as observed in our study, correlates with several pathologies associated with neuro-inflammation, and the reduction of cFOS gene expression may indicate the occurrence of reduced neuronal plasticity. Our study further extends our knowledge about the interaction of the immune system and the different forms of stress.
Assuntos
Citocinas , Peixe-Zebra , Animais , Encéfalo/metabolismo , Citocinas/genética , Citocinas/metabolismo , Neurônios/metabolismo , Estresse Psicológico/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
Methylphenidate (MPH) is a psychostimulant widely misused to increase wakefulness by drivers and students. Also, MPH can be found in dietary supplements in a clandestine manner aiming to burst performance of physical exercise practitioners. The abusive use of high doses of caffeine (CAF) in these contexts is equally already known. Here, we demonstrate the behavioral, oxidative and mitochondrial effects after acute exposure to high doses of MPH (80 mg/L) and CAF (150 mg/L), alone or associated (80 mg/L + 150 mg/L, respectively). We used zebrafish as animal model due to its high translational relevance. We evaluated the behavioral effects using the Novel Tank Test (NTT), Social Preference Test (SPT) and Y-maze Task and analyzed biomarkers of oxidative stress and activity of mitochondrial respiratory chain complexes. MPH alone induced antisocial behavior. MPH inhibited lipid peroxidation. The association of MPH + CAF presented memory impairment and anxiogenic behavior. In oxidative status, it inhibited lipid peroxidation, increased protein carbonylation and mitochondrial complex II, III and IV activity. Our results demonstrate that MPH and CAF alone negatively impact the typical behavioral of zebrafish. When associated, changes in cognition, memory, oxidative and mitochondrial status are more relevant.