Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En

Porto Alegre, Brazil

Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En

Porto Alegre, Brazil
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Rico E.P.,Federal University of Rio Grande do Sul | Rico E.P.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En | Rosemberg D.B.,Federal University of Rio Grande do Sul | Rosemberg D.B.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En | And 8 more authors.
Neurotoxicology and Teratology | Year: 2011

Recent advances in neurobiology have emphasized the study of brain structure and function and its association with numerous pathological and toxicological events. Neurotransmitters are substances that relay, amplify, and modulate electrical signals between neurons and other cells. Neurotransmitter signaling mediates rapid intercellular communication by interacting with cell surface receptors, activating second messenger systems and regulating the activity of ion channels. Changes in the functional balance of neurotransmitters have been implicated in the failure of central nervous system function. In addition, abnormalities in neurotransmitter production or functioning can be induced by several toxicological compounds, many of which are found in the environment. The zebrafish has been increasingly used as an animal model for biomedical research, primarily due to its genetic tractability and ease of maintenance. These features make this species a versatile tool for pre-clinical drug discovery and toxicological investigations. Here, we present a review regarding the role of different excitatory and inhibitory neurotransmitter systems in zebrafish, such as dopaminergic, serotoninergic, cholinergic, purinergic, histaminergic, nitrergic, glutamatergic, glycinergic, and GABAergic systems, and emphasizing their features as pharmacological and toxicological targets. The increase in the global knowledge of neurotransmitter systems in zebrafish and the elucidation of their pharmacological and toxicological aspects may lead to new strategies and appropriate research priorities to offer insights for biomedical and environmental research. © 2011 Elsevier Inc.


Oliveira R.D.L.,Grande Rio University | Oliveira R.D.L.,Instituto Nacional Of Ciencia E Tecnologia Translacional Em Medicina Inct Tm | Seibt K.J.,Grande Rio University | Seibt K.J.,Instituto Nacional Of Ciencia E Tecnologia Translacional Em Medicina Inct Tm | And 6 more authors.
Neurotoxicology and Teratology | Year: 2011

Lithium has been used as an effective antimanic drug in humans and it is well known for its effects on neuropsychiatric disorders and neuronal communication. ATP and adenosine are important signaling molecules, and most nerves release ATP as a fast co-transmitter together with classical neurotransmitters such as acetylcholine. In this study, we evaluated the in vitro and in vivo effects of lithium on acetylcholinesterase and ectonucleotidase activities in zebrafish brain. There was a significant inhibition of ADP hydrolysis after in vivo exposure to lithium at 5 and 10. mg/l (27.6% and 29% inhibition, respectively), whereas an inhibitory effect was observed for AMP hydrolysis only at 10. mg/l (30%). Lithium treatment in vivo also significantly decreased the acetylcholinesterase activity at 10. mg/l (21.9%). The mRNA transcript levels of the genes encoding for these enzymes were unchanged after exposure to 5 and 10. mg/l lithium chloride. In order to directly evaluate the action of lithium on enzyme activities, we tested the in vitro effect of lithium at concentrations ranging from 1 to 1000 μM. There were no significant changes in zebrafish brain ectonucleotidase and acetylcholinesterase activities at all concentrations tested in vitro. Our findings show that lithium treatment can alter ectonucleotidase and acetylcholinesterase activities, which may regulate extracellular nucleotide, nucleoside, and acetylcholine levels. These data suggest that cholinergic and purinergic signaling may be targets of the pharmacological effects induced by this compound. © 2011 Elsevier Inc.


Rosemberg D.B.,Federal University of Rio Grande do Sul | Rosemberg D.B.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En | Kist L.W.,Grande Rio University | Etchart R.J.,Grande Rio University | And 10 more authors.
Neuroscience Letters | Year: 2010

Taurine is one of the most abundant free amino acids in excitable tissues. In the brain, extracellular taurine may act as an inhibitory neurotransmitter, neuromodulator, and neuroprotector. Nucleotides are ubiquitous signaling molecules that play crucial roles for brain function. The inactivation of nucleotide-mediated signaling is controlled by ectonucleotidases, which include the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5'-nucleotidase. These enzymes hydrolyze ATP/GTP to adenosine/guanosine, which exert a modulatory role controlling several neurotransmitter systems. The nucleoside adenosine can be inactivated in extracellular or intracellular milieu by adenosine deaminase (ADA). In this report, we tested whether acute taurine treatment at supra-physiological concentrations alters NTPDase, ecto-5'-nucleotidase, and ADA activities in zebrafish brain. Fish were treated with 42, 150, and 400mgL -1 taurine for 1h, the brains were dissected and the enzyme assays were performed. Although the NTPDase activities were not altered, 150 and 400mgL -1 taurine increased AMP hydrolysis (128 and 153%, respectively) in zebrafish brain membranes and significantly decreased ecto-ADA activity (29 and 38%, respectively). In vitro assays demonstrated that taurine did not change AMP hydrolysis, whereas it promoted a significant decrease in ecto-ADA activity at 150 and 400mgL -1 (24 and 26%, respectively). Altogether, our data provide the first evidence that taurine exposure modulates the ecto-enzymes responsible for controlling extracellular adenosine levels in zebrafish brain. These findings could be relevant to evaluate potential beneficial effects promoted by acute taurine treatment in the central nervous system (CNS) of this species. © 2010 Elsevier Ireland Ltd.


Piato A.L.,Grande Rio University | Rosemberg D.B.,Federal University of Rio Grande do Sul | Capiotti K.M.,Grande Rio University | Capiotti K.M.,Instituto Nacional Of Ciencia E Tecnologia Translacional Em Medicina Inct Tm | And 11 more authors.
Neurochemical Research | Year: 2011

Despite the extensive knowledge about the effects of acute restraint stress (ARS) in rodents, zebrafish research is still elementary in this field, and the consequences of stress on purinergic system are unclear. Therefore, we evaluated the effects of ARS on behavior, biochemical, and molecular parameters in zebrafish brain. Animals were submitted to a 90 min ARS protocol and tested for anxiety levels, exploratory behavior, and memory performance. Furthermore, we analyzed ectonucleotidase and adenosine deaminase activities and their gene expression profile, as well as transcription of adenosinereceptors. ARS increased anxiety, but did not impair locomotion or cognition. ARS significantly increased ATP hydrolysis, decreased cytosolic ADA activity, and changed the entpd and adora gene expression. In conclusion, ARS disturbed zebrafish behavior, and we hypothesize that the augmentation in adenosine-mediated signaling may be a strategy to reestablish homeostasis and normal behavior after a stressful event. © Springer Science+Business Media, LLC 2011.


Menezes F.P.,Grande Rio University | Rico E.P.,Federal University of Rio Grande do Sul | Rico E.P.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En | Da Silva R.S.,Grande Rio University | Da Silva R.S.,Instituto Nacional Of Ciencia E Tecnologia Translacional Em Medicina Inct Tm
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2014

During brain development, the electrical disturbance promoted by a seizure can have several consequences, because it can disturb a set of steps extremely regulated needed to the correct brain maturation. Animal modeling of seizure is invaluable to contribute to the mechanistic understanding of punctual seizure event, and those that triggered in an immature neural network could alter the mature brain physiology. In the present study we observed that the exposure to kainic acid diluted directly in water of zebrafish decreased the locomotor activity at 7. days post-fertilization (dpf) animals and increased at 15. dpf, despite the absence of more specific seizure features. Pre-exposure to kainic acid (500. μM) diluted in water at 7. dpf animals reduced the susceptibility to a second exposure 2. months later by intraperitoneal injection. The current data suggest that these different responses are associated with neuronal maturation process and open a question about the window of development that are crucial to long lasting effects related to seizure in this animal model. © 2014 Elsevier Inc.


Blaser R.E.,University of San Diego | Rosemberg D.B.,Federal University of Rio Grande do Sul | Rosemberg D.B.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En
PLoS ONE | Year: 2012

The effects of wall color stimuli on diving, and the effects of depth stimuli on scototaxis, were assessed in zebrafish. Three groups of fish were confined to a black, a white, or a transparent tank, and tested for depth preference. Two groups of fish were confined to a deep or a shallow tank, and tested for black-white preference. As predicted, fish preferred the deep half of a split-tank over the shallow half, and preferred the black half of a black/white tank over the white half. Results indicated that the tank wall color significantly affected depth preference, with the transparent tank producing the strongest depth preference and the black tank producing the weakest preference. Tank depth, however, did not significantly affect color preference. Additionally, wall color significantly affected shuttling and immobility, while depth significantly affected shuttling and thigmotaxis. These results are consistent with previous indications that the diving response and scototaxis may reflect dissociable mechanisms of behavior. We conclude that the two tests are complementary rather than interchangeable, and that further research on the motivational systems underlying behavior in each of the two tests is needed. © 2012 Blaser, Rosemberg.


Zenki K.C.,Federal University of Rio Grande do Sul | Mussulini B.H.M.,Federal University of Rio Grande do Sul | Rico E.P.,Federal University of Rio Grande do Sul | Rico E.P.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao Inct En | And 5 more authors.
Toxicology in Vitro | Year: 2014

Ethanol (EtOH) and its metabolite, acetaldehyde (ALD), induce deleterious effects on central nervous system (CNS). Here we investigate the in vitro toxicity of EtOH and ALD (concentrations of 0.25%, 0.5%, and 1%) in zebrafish brain structures [telencephalon (TE), opticum tectum (OT), and cerebellum (CE)] by measuring the functionality of glutamate transporters, MTT reduction, and extracellular LDH activity. Both molecules decreased the activity of the Na+-dependent glutamate transporters in all brain structures. The strongest glutamate uptake inhibition after EtOH exposure was 58% (TE-1%), and after ALD, 91% (CE-1%). The results of MTT assay and LDH released demonstrated that the actions of EtOH and its metabolite are concentration and structure-dependent, in which ALD was more toxic than EtOH. In summary, our findings demonstrate a differential toxicity in vitro of EtOH and ALD in zebrafish brain structures, which can involve changes on glutamatergic parameters. We suggest that this species may be an interesting model for assessing the toxicological actions of alcohol and its metabolite in CNS. © 2014 Elsevier Ltd.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Benzecry R.,Federal University of Pará | Matos Oliveira K.R.,Federal University of Pará | And 10 more authors.
Behaviour | Year: 2012

The recent introduction of tasks to assess the behavior of zebrafish in novel and/or aversive environments has spurred great interest, prompting attempts to determine which constructs are modeled by these tasks (e.g., fear, anxiety, or some other construct). A review of the pharmacological and behavioral experiments indicates that not all behavioral testing models are equivalent. A more precise understanding of the parameters that influence task performance affords a wider selection of experimental procedures for investigating a particular construct, and also provides tools for differentiating the various constructs that may ultimately be of interest. In this review we will more closely examine two behavioral assays commonly used to measure the construct of 'anxiety' in adult zebrafish, with the conclusion that they do not both appear to be measuring a single underlying state. © 2012 Koninklijke Brill NV, Leiden.

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