Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-33772638

RESUMO

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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32800866

RESUMO

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.

3.
Environ Sci Pollut Res Int ; 27(31): 38559-38567, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32623676

RESUMO

Due to human activities, there is an increasing presence of agrochemicals residues in water bodies, which could be attributed to an increased use of these chemicals, incorrect disposal of packaging materials, and crop leaching. The effects of these residues on prey-predator relationship of aquatic animals are poorly known. Here, we show that fish acutely exposed to glyphosate, 2,4-D, and methylbenzoate-based agrichemicals have their anti-predatory responses impaired. We exposed zebrafish to sub-lethal concentrations of agrichemicals and evaluated their behavioral reaction against a simulated bird predatory strike. We observed that agrichemical-exposed fish spent more time in a risky area, suggesting that the pesticides interfered with their ability of risk perception. Our results highlight the impairment and environmental consequences of agrochemical residues, which can affect aquatic life and crucial elements for life (food web) such as the prey-predator relationship.


Assuntos
Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Agroquímicos , Animais , Cadeia Alimentar , Humanos , Comportamento Predatório
4.
Physiol Behav ; 222: 112944, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407833

RESUMO

Zebrafish has become an animal model in research and articles have established ideal conditions for their maintenance. However, little is known regarding the influence of gender and other cues on zebrafish behavior. Thus, here we analyzed the exploratory and social behavior of different sexes (male and female, mixed or segregated) under different housing conditions with various types of stimuli (visual or/and chemical cues and structural environmental enrichment). Segregated females and males were more active than mixed individuals and females were more anxious. Fish that visualized and smelled the opposite sex presented higher activity and were less anxious than individuals that only smelled or visualized the opposite sex. Fish segregated by sex while being allowed to visualize and smell the opposite sex with the presence of structural environmental enrichment exhibited lower activity and anxiety-like behavior than fish without structural environmental enrichment. Thus, we emphasized that these variables should be taken into account in housing conditions and should be detailed for better replicability and reproducibility of experiments performed with zebrafish.

5.
Environ Sci Pollut Res Int ; 26(25): 26293-26303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286368

RESUMO

Since behavior is the connection between the internal physiological processes of an animal and its interaction with the environment, a complete behavioral repertoire is crucial for fish survival and fitness, at both the individual and population levels. Thus, unintended exposure of non-target organisms to antipsychotic residues in the environment can impact their normal behavior, and some of these behavioral changes can be seen during the entire life of the animal and passed to subsequent generations. Although there are some reports related to transgenerational toxicology, little is known of the long-term consequences of exposure to pharmaceutical compounds such as risperidone. Here, we show that zebrafish exposed to risperidone (RISP) during embryonic and larval stages presented impaired anti-predatory behavior during adulthood, characterizing a persistent effect. We also show that some of these behavioral changes are present in the following generation, characterizing a transgenerational effect. This suggests that even short exposures to environmentally relevant concentrations, at essential stages of development, can persist throughout the whole life of the zebrafish, including its offspring. From an environmental perspective, our results suggested possible risks and long-term consequences associated with drug residues in water, which can affect aquatic life and endanger species that depend on appropriate behavioral responses for survival.


Assuntos
Risperidona/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Comportamento Animal/efeitos dos fármacos , Ecotoxicologia/métodos , Embrião não Mamífero/efeitos dos fármacos , Feminino , Larva/efeitos dos fármacos , Masculino , Comportamento Predatório/efeitos dos fármacos , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologia
6.
Brain Behav Immun ; 73: 596-602, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29981831

RESUMO

In a previous study we showed a clear relationship between immune system and behavior in zebrafish and we hypothesized that the immune system is capable of inducing behavioral changes. To further investigate this subject and to address our main question, here we induced an inflammatory response in one group of fish by the inoculation of formalin-inactivated Aeromonoas hydrophila bacterin and compared their social and exploratory behavior with control groups. After the behavioral tests, we also analyzed the expression of cytokines genes and markers of neuronal activity in fish brain. In the bacterin-inoculated fish, the locomotor activity, social preference and exploratory behavior towards a new object were reduced compared to the control fish while the expression of proinflammatory cytokines in the brain was upregulated. With this study we demonstrated for the first time that the immune system is capable of causing behavioral changes that are consistent with the sickness behavior observed in mammals.


Assuntos
Comportamento de Doença/fisiologia , Peixe-Zebra/imunologia , Peixe-Zebra/fisiologia , Animais , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Feminino , Sistema Imunitário/metabolismo , Relações Interpessoais , Locomoção/imunologia , Locomoção/fisiologia , Masculino , Atividade Motora/fisiologia , Neurônios/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-26025319

RESUMO

Chronic pain and depression are two complex states that often coexist in the clinical setting and traditional antidepressants and analgesics have shown limited clinical efficacy. There is an intricate communication between the immune system and the central nervous system and inflammation has been considered a common mediator of pain-depression comorbidity. This study evaluated the effect of m-trifluoromethyl diphenyl diselenide [(m-CF3-PhSe)2], an organoselenium compound that has been reported to have both antinociceptive and antidepressant-like actions, in the comorbidity of chronic pain and depression induced by partial sciatic nerve ligation (PSNL) in an inflammatory approach. Mice were submitted to PSNL during 4weeks and treated with (m-CF3-PhSe)2 acutely (0.1-10mg/kg, i.g.) or subchronically (0.1mg/kg, i.g., once a day during the 3rd and 4th weeks). Both treatments prevented PSNL-increased pain sensitivity and depressive-like behavior observed in Von-Frey hair (VFH) and forced swimming (FST) tests, respectively. These effects could be mainly associated with an anti-inflammatory action of (m-CF3-PhSe)2 which reduced the levels of pro-inflammatory cytokines, NF-κB and COX-2, and p38 MAPK activation that were increased by PSNL. (m-CF3-PhSe)2 also increased the BDNF levels and reduced glutamate release and 5-HT uptake altered by PSNL. Although acute and subchronic treatments with (m-CF3-PhSe)2 prevented these alterations induced by PSNL, the best results were found when (m-CF3-PhSe)2 was subchronically administered to mice. Considering the potential common mechanisms involved in the comorbidity of inflammation-induced depression and chronic pain, the results found in this study indicate that (m-CF3-PhSe)2 could become an interesting molecule to treat long-lasting pathological pain associated with depression.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/prevenção & controle , Neuralgia/complicações , Neuralgia/psicologia , Compostos de Organossilício/uso terapêutico , Hormônio Adrenocorticotrópico/sangue , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Corticosterona/sangue , Citocinas/sangue , Depressão/complicações , Modelos Animais de Doenças , Lateralidade Funcional , Ácido Glutâmico/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neuralgia/etiologia , Traumatismos dos Nervos Periféricos/complicações , Serotonina/metabolismo , Natação/psicologia , Sinaptossomos/metabolismo , Trítio/metabolismo
8.
J Psychiatr Res ; 66-67: 75-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25982254

RESUMO

A growing body of evidence associates activation of immune system with depressive symptoms. Accordingly, pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), have been shown to play a pivotal role in the pathophysiology of depression. The aim of this study was to evaluate the effectiveness of acute and subchronic treatments with (m-CF3-PhSe)2 to prevent the depressive-like behavior induced by intracerebroventricular injection of TNF-α in mice. TNF-α induced depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST) (0.1 and 0.001 ƒg/5 µL/site, respectively) without changing locomotor activity, performed in the locomotor activity monitor (LAM). Acute (0.01-50 mg/kg; intragastric (i.g.); 30 min) and subchronic (0.01 and 0.1 mg/kg; i.g.; 14 days) treatments with (m-CF3-PhSe)2 at low doses were effective against the effect of TNF-α in the FST and TST. Nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK), important proteins in TNF-activated signaling, were determined in the prefrontal cortex and hippocampus of mouse. TNF-α (0.1 ƒg/5 µL/site) increased NF-κB levels and p38 MAPK activation in both brain areas and acute (10 mg/kg; i.g.) and subchronic (0.01 mg/kg; i.g.) treatments with (m-CF3-PhSe)2 were effective in attenuating this increase. Although more studies are necessary to indicate this compound as a therapeutic alternative to depression, the antidepressant-like and anti-inflammatory effects of (m-CF3-PhSe)2 demonstrated herein may support it as an interesting molecule in the search for new drugs to treat depressive disorders that have been largely linked to immune process and inflammation.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/tratamento farmacológico , Compostos de Organossilício/farmacologia , Animais , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , NF-kappa B/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Fator de Necrose Tumoral alfa , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Curr Pharm Des ; 21(7): 920-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25312723

RESUMO

Ebselen is a synthetic organoselenium compound that has been considered a potential pharmacological agent with low toxicity, showing antioxidant, anti-inflammatory and neuroprotective effects. It is bioavailable, blood-brain barrier permeant and safe based on cellular toxicity and Phase I-III clinical trials. There is evidence that ebselen inhibits acetylcholinesterase (AChE) activity, an enzyme that plays a key role in the cholinergic system by hydrolyzing acetylcholine (ACh), in vitro and ex vivo. This system has a well-known relationship with cognitive process, and AChE inhibitors, such as donepezil and galantamine, have been used to treat cognitive deficits, mainly in the Alzheimer's Disease (AD). However, these drugs have poor bioavailability and a number of side effects, including gastrointestinal upsets and hepatotoxicity. In this way, this study aimed to evaluate the effect of ebselen on cerebral AChE activity in vitro and to determine the kinetic profile and the reversibility of inhibition by dialysis. Ebselen inhibited the cerebral AChE activity with an IC50 of 29 µM, similar to IC50 found with pure AChE from electric eel, demonstrating a mixed and reversible inhibition of AChE, since it increased Km and decreased Vmax. The AChE activity was recovered within 60 min of dialysis. Therefore, the use of ebselen as a therapeutic agent for treatment of AD should be considered, although memory behavior tasks are needed to support such hypothesis.


Assuntos
Azóis/farmacocinética , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Inibidores da Colinesterase/farmacocinética , Compostos Organosselênicos/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Antioxidantes/farmacocinética , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/enzimologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Masculino , Ratos , Ratos Wistar
10.
Pharmacol Biochem Behav ; 125: 15-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25135115

RESUMO

The organoselenium compound m-trifluoromethyl diphenyl diselenide (m-CF3-PhSe)2 has antinociceptive actions in several animal models, which are mediated by interaction with endogenous opioid systems. It also shows antidepressant-like action mediated by both opioid and serotonergic systems. Considering that serotonin (5-HT) plays an important role in the descending control of pain, this study further investigated the role of serotonergic systems in the antinociceptive action of (m-CF3-PhSe)2 in the glutamate-induced licking behavior model in mice. (m-CF3-PhSe)2 (1-50 mg/kg, p.o.), morphine (2.5 mg/kg, s.c.) or paroxetine (5 mg/kg, i.p.) reduced glutamate-induced nociception. Selective 5-HT1A and 5-HT2A receptor antagonists, WAY100635 (0.7 mg/kg, i.p.) and ketanserin (0.3 mg/kg, i.p.), but not the selective 5-HT3 receptor antagonist, ondansetron (0.5 mg/kg, i.p.), prevented the antinociceptive effect of (m-CF3-PhSe)2 (10 mg/kg) in the glutamate test. In biochemical studies, (m-CF3-PhSe)2 (10 and 50 mg/kg) decreased [(3)H]5-HT uptake in crude synaptosomes of mouse brains and slightly inhibited in vitro [(3)H]5-HT binding. In kinetic studies, the selenium (Se) distribution was determined at different time points after the administration of (m-CF3-PhSe)2 (500 mg/kg, p.o.) to mice. After 30 min, a high amount of Se was found in liver and kidneys, followed by the lung, red blood cells, serum and brain. A significant amount of Se accumulated in fat over the course of 8h. Urine was an important route of Se excretion originating from (m-CF3-PhSe)2. Collectively, results of this study indicate an involvement of the serotonergic systems in the antinociceptive effect of (m-CF3-PhSe)2 and a wide distribution of Se derived from this compound.


Assuntos
Analgésicos/farmacologia , Ácido Glutâmico , Compostos de Organossilício/farmacologia , Dor/tratamento farmacológico , Neurônios Serotoninérgicos/efeitos dos fármacos , Animais , Feminino , Camundongos , Medição da Dor , Selênio/análise , Serotonina/metabolismo , Sinaptossomos/metabolismo , Distribuição Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...