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1.
Curr Neuropharmacol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588731

RESUMO

Schizophrenia pathophysiology is associated with hypofunction of glutamate NMDA receptors (NMDAR) in GABAergic interneurons and dopaminergic hyperactivation in subcortical brain areas. The administration of NMDAR antagonists is used as an animal model that replicates behavioral phenotypes relevant to the positive, negative, and cognitive symptoms of schizophrenia. Such models overwhelmingly rely on rodents, which may lead to species-specific biases and poor translatability. Zebrafish, however, is increasingly used as a model organism to study evolutionarily conserved aspects of behavior. We thus aimed to review and integrate the major findings reported in the zebrafish literature regarding the behavioral effects of NMDAR antagonists with relevance to schizophrenia. We identified 44 research articles that met our inclusion criteria from 590 studies retrieved from MEDLINE (PubMed) and Web of Science databases. Dizocilpine (MK-801) and ketamine were employed in 29 and 10 studies, respectively. The use of other NMDAR antagonists, such as phencyclidine (PCP), APV, memantine, and tiletamine, was described in 6 studies. Frequently reported findings are the social interaction and memory deficits induced by MK-801 and circling behavior induced by ketamine. However, mixed results were described for several locomotor and exploratory parameters in the novel tank and open tank tests. The present review integrates the most relevant results while discussing variation in experimental design and methodological procedures. We conclude that zebrafish is a suitable model organism to study drug-induced behavioral phenotypes relevant to schizophrenia. However, more studies are necessary to further characterize the major differences in behavior as compared to mammals.

2.
Environ Sci Pollut Res Int ; 27(36): 45874-45882, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32803608

RESUMO

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most commonly used herbicides worldwide. While the effects of 2,4-D in target organisms are well known, its consequences in nontarget organisms are not fully explained. Therefore, the purpose of this study was to investigate the effects of the herbicide on mitochondrial energy metabolism, oxidative status, and exploratory behavior in adult zebrafish. Animal exposure to 2,4-D increased cytochrome c oxidase and catalase activities and reduced SOD/CAT ratio, moreover, increased the total distance traveled and the number of crossings. Finally, animals exposed to 2,4-D spent more time in the upper zone of the tank and traveled a long distance in the upper zone. Overall, our results indicate the 2,4-D can provoke disabling effects in nontarget organisms. The obtained data showed that exposure to 2,4-D at environmentally relevant concentrations alters mitochondrial metabolism and antioxidant status and disturbs the zebrafish innate behavior.


Assuntos
Herbicidas , Peixe-Zebra , Ácido 2,4-Diclorofenoxiacético/toxicidade , Animais , Herbicidas/toxicidade , Mitocôndrias , Estresse Oxidativo
3.
Naunyn Schmiedebergs Arch Pharmacol ; 393(7): 1303-1311, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32363414

RESUMO

Preclinical evidence on the role of glucagon-like peptide-1 receptor (GLP-1r) agonists in the brain led to an increased interest in repurposing these compounds as a therapy for central nervous system (CNS) disorders and associated comorbidities. We aimed to investigate the neuroprotective effects of acute treatment with exendin (EX)-4, a GLP-1r agonist, in an animal model of inflammation. We evaluated the effect of different doses of EX-4 on inflammatory, neurotrophic, and oxidative stress parameters in the hippocampus and serum of lipopolysaccharide (LPS)-injected animals. Male Wistar rats were injected with LPS (0.25 mg/kg i.p.) and treated with different doses of EX-4 (0.1, 0.3, or 0.5 µg/kg i.p.). Sickness behavior was assessed by locomotor activity and body weight, and depressive-like behavior was also evaluated using forced swim test (FST). Brain-derived neurotrophic factor (BDNF), thiobarbituric acid reactive species (TBARS), and interleukin (IL)-6 were quantified in the serum and hippocampus. Glycemia was also analyzed pre- and post-EX-4 treatment. LPS groups exhibited decreased frequency of crossing and reduced body weight (p < 0.001), while alterations on FST were not observed. The higher dose of EX-4 reduced IL-6 in the hippocampus of LPS-injected animals (p = 0.018), and EX-4 per se reduced TBARS serum levels with a modest antioxidant effect in the LPS groups (p ≤ 0.005). BDNF hippocampal levels seemed to be increased in the LPS+EX-4 0.5 group compared with LPS+Saline (p > 0.05). Our study provides evidence on acute anti-inflammatory effects of EX-4 in the hippocampus of rats injected with LPS, contributing to future studies on repurposing compounds with potential neuroprotective properties.

4.
Pharmacol Biochem Behav ; 193: 172928, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32289330

RESUMO

Acute and chronic stressors are common triggers of human mental illnesses. Experimental animal models and their cross-species translation to humans are critical for understanding of the pathogenesis of stress-related psychiatric disorders. Mounting evidence suggests that both pharmacological and non-pharmacological approaches can be efficient in treating these disorders. Here, we analyze human, rodent and zebrafish (Danio rerio) data to compare the impact of non-pharmacological and pharmacological therapies of stress-related psychopathologies. Emphasizing the likely synergism and interplay between pharmacological and environmental factors in mitigating daily stress both clinically and in experimental models, we argue that environmental enrichment emerges as a promising complementary therapy for stress-induced disorders across taxa. We also call for a broader use of novel model organisms, such as zebrafish, to study such treatments and their potential interplay.

5.
Ecotoxicology ; 29(2): 140-147, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31865514

RESUMO

Pesticide commercial mixtures, including the insecticide fipronil and the fungicides pyraclostrobin and methyl-thiophanate, have been used in concomitant pest control, facilitating agricultural management. Their widespread use can lead to soil and water contamination and potentially induce damages in the ecosystem, producing toxic effects in non-target organisms. Despite their toxicological potential, their effects on behavioral and biochemical parameters are not well understood. Here we investigated the effects of the mixture of fipronil and fungicides (MFF) pyraclostrobin and methyl- thiophanate on behavioral and biochemical parameters of oxidative stress in adult zebrafish. Animals exposed to the highest MFF tested concentration showed a decrease in the total distance traveled and in the number of crossings in the different zones of the tank. Furthermore, animals exposed to highest MFF tested concentration spent more time in water surface. In addition, our data showed that the exposure to this preparation promoted a decrease in non-protein thiol content as well as in catalase activity. Finally, pesticide exposure induced an increase in the superoxide dismutase/catalase ratio. Our results indicate that alterations in behavioral and oxidative parameters are involved in MFF toxicity in zebrafish. The antioxidant mechanisms analyzed were altered in concentrations that did not affect zebrafish behavior. Therefore, the assessment of oxidative stress parameters in zebrafish brains could be very useful to detect the early effects of environmental exposure to the MFF.


Assuntos
Pirazóis/toxicidade , Peixe-Zebra/fisiologia , Animais , Antioxidantes , Comportamento Animal/fisiologia , Fungicidas Industriais , Estresse Oxidativo/fisiologia , Poluentes Químicos da Água/toxicidade
6.
Naunyn Schmiedebergs Arch Pharmacol ; 393(4): 591-601, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31768573

RESUMO

Anxiety disorders are highly prevalent and a leading cause of disability worldwide. Their etiology is related to stress, an adaptive response of the organism to restore homeostasis, in which oxidative stress and glutamatergic hyperactivity are involved. N-Acetylcysteine (NAC) is a multitarget approved drug proved to be beneficial in the treatment of various mental disorders. Nevertheless, NAC has low membrane permeability and poor bioavailability and its limited delivery to the brain may explain inconsistencies in the literature. N-Acetylcysteine amide (AD4) is a synthetic derivative of NAC in which the carboxyl group was modified to an amide. The amidation of AD4 improved lipophilicity and blood-brain barrier permeability and enhanced its antioxidant properties. The purpose of this study was to investigate the effects of AD4 on behavioral and biochemical parameters in zebrafish anxiety models. Neither AD4 nor NAC induced effects on locomotion and anxiety-related parameters in the novel tank test. However, in the light/dark test, AD4 (0.001 mg/L) increased the time spent in the lit side in a concentration 100 times lower than NAC (0.1 mg/L). In the acute restraint stress protocol, NAC and AD4 (0.001 mg/L) showed anxiolytic properties without meaningful effects on oxidative status. The study suggests that AD4 has anxiolytic effects in zebrafish with higher potency than the parent compound. Additional studies are warranted to characterize the anxiolytic profile of AD4 and its potential in the management of anxiety disorders.

7.
Behav Brain Res ; 378: 112264, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568833

RESUMO

Stressful experiences are related to the triggering of anxiety and mood disorders. Tryptophan (amino acid precursor of serotonin synthesis) emerges as important treatment of these disorders. Here, we evaluate the effects of pre-treatment with tryptophan (300 mg/L) and fluoxetine (50 µg/L) in response to acute stress in zebrafish. Overall, acute stress decreased the distance traveled, entries and time in top of tank, as well as increased the cortisol levels, demonstrating an anxiogenic behavior. Tryptophan and fluoxetine prevented anxiogenic effects. This study showed the importance of tryptophan and fluoxetine in the regulation of stress and anxiety-like behavior in adult zebrafish. Collectively, our data support tryptophan effects on stress responses in zebrafish and reinforce the growing utility of this aquatic model to screen CNS therapies.

8.
Environ Sci Pollut Res Int ; 26(27): 27808-27815, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342352

RESUMO

The use of pesticides has been growing along with the demand for agricultural products. These compounds, however, are not restricted to the field, spreading easily through the soil, contaminating groundwater and reaching urban centers. Propiconazole is a triazole fungicide that has been increasingly used in agriculture. However, there are few data about its effects on non-target organisms. This study aimed to evaluate the effects of propiconazole in zebrafish. The animals were exposed for 96 h to different concentrations of propiconazole (425, 850, 1700, 8500 ng/L), then submitted to the novel tank test for behavioral analyses. The brains were collected for evaluation of oxidative stress parameters. Exposure to propiconazole (1700 and 8500 ng/L) decreased the number of crossings, entries, and time spent in the top, and increased the time spent in the bottom area of the tank. We also observed an increase in the activities of superoxide dismutase and catalase in zebrafish brain exposed to propiconazole at 425, 850, and 1700 ng/L. We conclude that propiconazole alters normal fish behavior and disrupts oxidative status. More studies are necessary to elucidate the exact mechanism underlying the effects of propiconazole on non-target-organisms.


Assuntos
Catalase/química , Fungicidas Industriais/análise , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/química , Triazóis/análise , Agricultura , Animais , Fungicidas Industriais/química , Água Subterrânea , Praguicidas/análise , Praguicidas/química , Solo , Triazóis/química , Peixe-Zebra
9.
Artigo em Inglês | MEDLINE | ID: mdl-30946939

RESUMO

Alcohol abuse is a highly prevalent condition that substantially contributes to global morbidity and mortality. Most available pharmacological treatments offer little efficacy as relapse rates are high, due in part to the symptoms experienced during abstinence. The roles of oxidative stress and glutamatergic transmission in alcohol withdrawal have been demonstrated in several studies, suggesting that restoration of oxidative status and glutamatergic function may represent a new pharmacological target to prevent the behavioral and biochemical alterations observed during withdrawal. A well-known antioxidant and glutamatergic modulator, N-acetylcysteine (NAC), has shown promise in treating a variety of psychiatric conditions, including substance use disorders, and is a promising molecule in the management of alcohol withdrawal syndrome. Thus, the aim of this study was to investigate whether NAC is able to prevent the expression of behavioral and biochemical alterations induced by ethanol withdrawal in chronically exposed zebrafish. Animals were exposed to ethanol (1% v/v, 20 min) or control water, followed by treatment with NAC (1 mg/L, 10 min) or control water daily for 8 days; 24 h later, experimental animals were submitted to the novel tank test (NTT). Ethanol withdrawal decreased the distance traveled and increased the number of immobile episodes, indicating locomotor deficits; moreover, withdrawal decreased the number of entries and time spent in the top area, while increasing time spent in the bottom area, indicating anxiety-like behavior. Alcohol withdrawal also increased lipid peroxidation (TBARS) and decreased non-protein reduced sulfhydryl (NPSH) and superoxide dismutase (SOD) and catalase (CAT) activities. NAC attenuated these locomotor deficits and prevented the manifestation of anxiety-like behavior as well as the oxidative damage observed following ethanol withdrawal. Given its favorable safety profile, additional clinical and preclinical studies are warranted to unravel the long-term effects of NAC in the context of alcohol abuse and the exact mechanisms involved. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in substance abuse disorders.


Assuntos
Acetilcisteína/uso terapêutico , Etanol/efeitos adversos , Síndrome de Abstinência a Substâncias/prevenção & controle , Animais , Ansiedade/induzido quimicamente , Ansiedade/prevenção & controle , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Peixe-Zebra
10.
Rev. bras. psiquiatr ; 41(2): 168-178, Mar.-Apr. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-990820

RESUMO

Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.


Assuntos
Humanos , Animais , Transtornos de Ansiedade/tratamento farmacológico , Acetilcisteína/farmacologia , Ansiolíticos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Hipnóticos e Sedativos/farmacologia , Acetamidas/farmacologia , Neuroimunomodulação/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , Glutamina/efeitos dos fármacos
11.
Neuropharmacology ; 150: 145-152, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30917915

RESUMO

Stress-related psychiatric disorders are mental conditions that affect mood, cognition and behavior and arise because of the impact of prolonged stress on the central nervous system (CNS). Acetyl-L-carnitine (ALC) is an acetyl ester of L-carnitine that easily crosses the blood-brain barrier and was recently found to be decreased in patients with major depressive disorder. ALC plays a role in energy metabolism and is widely consumed as a nutritional supplement to improve physical performance. In this study, our objective was to evaluate the effects of ALC treatment (0.1 mg/L, 10 min) for 7 days on behavior and oxidative stress in zebrafish subjected to unpredictable chronic stress (UCS) protocol. Behavioral outcomes were assessed in the novel tank test, and parameters of oxidative status (lipid peroxidation and antioxidant defenses) were evaluated in the brain using colorimetric methods. According to our previous findings, UCS increased anxiety-like behavior and lipid peroxidation, while it decreased non-protein thiol levels and superoxide dismutase activity. However, ALC reversed the anxiety-like behavior and oxidative damage in stressed animals, while it was devoid of effect in control animals. Although our data reinforce the neuroprotective potential of ALC in the treatment of psychiatric disorders related to stress, further investigations are required to clarify its mechanisms of action and confirm its efficacy.


Assuntos
Acetilcarnitina/farmacologia , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Acetilcarnitina/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Encéfalo/metabolismo , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Peixe-Zebra
12.
Mol Neurobiol ; 56(2): 1188-1195, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29876880

RESUMO

There is accumulating evidence on the use of N-acetylcysteine (NAC) in the treatment of patients with neuropsychiatric disorders. As a multi-target drug and a glutathione precursor, NAC is a promising molecule in the management of stress-related disorders, for which there is an expanding field of research investigating novel therapies targeting oxidative pathways. The deleterious effects of chronic stress in the central nervous system are a result of glutamatergic hyperactivation, glutathione (GSH) depletion, oxidative stress, and increased inflammatory response, among others. The aim of this study was to investigate the effects of NAC in zebrafish submitted to unpredictable chronic stress (UCS). Animals were initially stressed or not for 7 days, followed by treatment with NAC (1 mg/L, 10 min) or vehicle for 7 days. UCS decreased the number of entries and time spent in the top area in the novel tank test, which indicate increased anxiety levels. It also increased reactive oxygen species (ROS) levels and lipid peroxidation (TBARS) while decreased non-protein thiols (NPSH) and superoxide dismutase (SOD) activity. NAC reversed the anxiety-like behavior and oxidative damage observed in stressed animals. Additional studies are needed to investigate the effects of this agent on glutamatergic modulation and inflammatory markers related to stress. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in mood disorders, anxiety, post-traumatic stress disorder, and other conditions associated with stress.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Acetilcisteína/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Ansiedade/metabolismo , Encéfalo/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estresse Psicológico/metabolismo , Superóxido Dismutase/metabolismo , Peixe-Zebra
13.
Braz J Psychiatry ; 41(2): 168-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30328963

RESUMO

OBJECTIVE: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. METHODS: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. RESULTS: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. CONCLUSION: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.


Assuntos
Acetamidas/farmacologia , Acetilcisteína/farmacologia , Ansiolíticos/farmacologia , Transtornos de Ansiedade/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Hipnóticos e Sedativos/farmacologia , Animais , Modelos Animais de Doenças , Glutamina/efeitos dos fármacos , Humanos , Neuroimunomodulação/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
14.
Sci Rep ; 8(1): 13908, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30224742

RESUMO

Here we show that the novel object recognition test can discriminate between high (HRN, neophobic) and low (LRN, neophilic) novelty responders in zebrafish populations. Especially when we observe the latency to the first entry in the novel object zone, zebrafish did not maintain these behavioral phenotypes in sequential tests and only the HRN group returned to their initial responsive behavior when exposed to fluoxetine. Our results have important implications for behavioral data analysis since such behavioral differences can potentially increase individual response variability and interfere with the outcomes obtained from various behavioral tasks. Our data reinforce the validity of personality determination in zebrafish since we show clear differences in behavior in response to fluoxetine.


Assuntos
Comportamento Animal/efeitos dos fármacos , Fluoxetina/farmacologia , Peixe-Zebra/fisiologia , Animais , Masculino
15.
PeerJ ; 6: e5343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30090692

RESUMO

Here we show that the feeding regimen modulates zebrafish (Danio rerio) behavior. With regard to the time elapsed between feeding and behavioral evaluation, fish fed 3 h before behavioral evaluation in the novel tank test (NTT) showed decreased activity and a trend toward an anxiolytic reaction (increased use of the upper section of the aquarium) in comparison to fish fed 0.5, 6, 12, 24 or 48 h before testing, although differences were not statistically significant for all comparisons. Activity and use of the upper section of the aquarium did not differ significantly among the other treatments. Regarding feeding frequency, fish fed once a day showed higher anxiety-like behavior (decreased use of the upper section of the aquarium) in comparison to fish fed twice a day, but feeding four or six times per day or only every second day did not result in differences from feeding twice a day. Feeding frequency had no effect on activity level. Metabolically, fish fed once a day presented decreased levels of glucose and glycogen and increased lactate when compared to the regular feeding (fish fed twice a day), suggesting that feeding regimen may modulate carbohydrate metabolism. Mechanistically, we suggest that the metabolic changes caused by the feeding regimen may induce behavioral changes. Our results suggest that the high variability of the results among different laboratories might be related to different feeding protocols. Therefore, if issues pertaining to the feeding regimen are not considered during experiments with zebrafish, erroneous interpretations of datasets may occur.

16.
PeerJ ; 6: e5309, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30083453

RESUMO

Studies have suggested that oxidative stress may contribute to the pathogenesis of mental disorders. In this context, molecules with antioxidant activity may be promising agents in the treatment of these deleterious conditions. Acetyl-L-carnitine (ALC) is a multi-target molecule that modulates the uptake of acetyl-CoA into the mitochondria during fatty acid oxidation, acetylcholine production, protein, and membrane phospholipid synthesis, capable of promoting neurogenesis in case of neuronal death. Moreover, neurochemical effects of ALC include modulation of brain energy and synaptic transmission of multiple neurotransmitters, including expression of type 2 metabotropic glutamate (mGlu2) receptors. The aim of this study was to investigate the effects of ALC in zebrafish by examining behavioral and biochemical parameters relevant to anxiety and mood disorders in zebrafish. ALC presented anxiolytic effects in both novel tank and light/dark tests and prevented the anxiety-like behavior induced by an acute stressor (net chasing). Furthermore, ALC was able to prevent the lipid peroxidation induced by acute stress in the zebrafish brain. The data presented here warrant further investigation of ALC as a potential agent in the treatment of neuropsychiatric disorders. Its good tolerability also subsidizes the additional studies necessary to assess its therapeutic potential in clinical settings.

17.
PeerJ ; 6: e5136, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30002970

RESUMO

Background: The enriched environment (EE) is a laboratory housing model that emerged from efforts to minimize the impact of environmental conditions on laboratory animals. Recently, we showed that EE promoted positive effects on behavior and cortisol levels in zebrafish submitted to the unpredictable chronic stress (UCS) protocol. Here, we expanded the characterization of the effects of UCS protocol by assessing parameters of oxidative status in the zebrafish brain and reveal that EE protects against the oxidative stress induced by chronic stress. Methods: Zebrafish were exposed to EE (21 or 28 days) or standard housing conditions and subjected to the UCS protocol for seven days. Oxidative stress parameters (lipid peroxidation (TBARS), reactive oxygen species (ROS) levels, non-protein thiol (NPSH) and total thiol (SH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were measured in brain homogenate. Results: Our results revealed that UCS increased lipid peroxidation and ROS levels, while decreased NPSH levels and SOD activity, suggesting oxidative damage. EE for 28 days prevented all changes induced by the UCS protocol, and EE for 21 days prevented the alterations on NPSH levels, lipid peroxidation and ROS levels. Both EE for 21 or 28 days increased CAT activity. Discussion: Our findings reinforce the idea that EE exerts neuromodulatory effects in the zebrafish brain. EE promoted positive effects as it helped maintain the redox homeostasis, which may reduce the susceptibility to stress and its oxidative impact.

18.
PeerJ ; 6: e4957, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868300

RESUMO

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extra-synaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet. Methods: In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish. Results: NAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects. Discussion: NAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.

19.
J Exp Biol ; 221(Pt 4)2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29361609

RESUMO

Several studies have shown that manipulations to the housing environment modulate susceptibility to stress in laboratory animals, mainly in rodents. Environmental enrichment (EE) is one such manipulation that promotes neuroprotection and neurogenesis, besides affecting behaviors such as drug self-administration. Zebrafish are a popular and useful animal model for behavioral neuroscience studies; however, studies evaluating the impact of housing conditions in this species are scarce. In this study, we verified the effects of EE on behavioral (novel tank test) and biochemical [cortisol and reactive oxygen species (ROS)] parameters in zebrafish submitted to unpredictable chronic stress (UCS). Consistent with our previous findings, UCS increased anxiety-like behavior, cortisol and ROS levels in zebrafish. EE for 21 or 28 days attenuated the effects induced by UCS on behavior and cortisol, and prevented the effects on ROS levels. Our findings reinforce the idea that EE exerts neuromodulatory effects across species, reducing vulnerability to stress and its biochemical impact. Also, these results indicate that zebrafish is a suitable model animal to study the behavioral effects and neurobiological mechanisms related to EE.


Assuntos
Bem-Estar do Animal , Meio Ambiente , Estresse Fisiológico , Peixe-Zebra/fisiologia , Animais , Feminino , Abrigo para Animais , Hidrocortisona/metabolismo , Masculino , Modelos Animais , Distribuição Aleatória , Espécies Reativas de Oxigênio/metabolismo
20.
Neurosci Lett ; 664: 34-37, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29126775

RESUMO

We examined whether lithium carbonate (Li2CO3, 100mg/L) is able to prevent memory impairment induced by scopolamine. Moreover, we evaluated the effects of lithium on anxiety-like behavior and acetylcholinesterase activity in adult zebrafish. We demonstrated that lithium prevents the memory impairment induced by scopolamine, decreases exploration and increases the activity of acetylcholinesterase in zebrafish. Collectively, this contributes to a better understanding of the pharmacology of lithium, its interaction with cholinergic neurotransmission, and its possible application to therapeutic treatments aimed at improving cognition.


Assuntos
Carbonato de Lítio/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Escopolamina/toxicidade , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Carbonato de Lítio/farmacologia , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/psicologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Antagonistas Muscarínicos/toxicidade , Peixe-Zebra
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