Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao

Porto Alegre, Brazil

Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao

Porto Alegre, Brazil

Time filter

Source Type

Schmidel A.J.,Chapecó Region Community University | Assmann K.L.,Chapecó Region Community University | Werlang C.C.,Chapecó Region Community University | Bertoncello K.T.,Chapecó Region Community University | And 13 more authors.
Neurotoxicology and Teratology | Year: 2014

Animal behaviour is the interaction between environment and an individual organism, which also can be influenced by its neighbours. Variations in environmental conditions, as those caused by contaminants, may lead to neurochemical impairments altering the pattern of the behavioural repertoire of the species. Atrazine (ATZ) is an herbicide widely used in agriculture that is frequently detected in surface water, affecting non-target species. The zebrafish is a valuable model organism to assess behavioural and neurochemical effects of different contaminants since it presents a robust behavioural repertoire and also all major neurotransmitter systems described for mammalian species. The goal of this study was to evaluate the effects of subchronic ATZ exposure in defensive behaviours of zebrafish (shoaling, thigmotaxis, and depth preference) using the split depth tank. Furthermore, to investigate a putative role of cholinergic signalling on ATZ-mediated effects, we tested whether this herbicide alters acetylcholinesterase (AChE) activity in brain and muscle preparations. Fish were exposed to ATZ for 14. days and the following groups were tested: control (0.2% acetone) and ATZ (10 and 1000. μg/L). The behaviour of four animals in the same tank was recorded for 6. min and biological samples were prepared. Our results showed that 1000. μg/L ATZ significantly increased the inter-fish distance, as well as the nearest and farthest neighbour distances. This group also presented an increase in the shoal area with decreased social interaction. No significant differences were detected for the number of animals in the shallow area, latency to enter the shallow and time spent in shallow and deep areas of the apparatus, but the ATZ 1000 group spent significantly more time near the walls. Although ATZ did not affect muscular AChE, it significantly reduced AChE activity in brain. Exposure to 10. μg/L ATZ did not affect behaviour or AChE activity. These data suggest that ATZ impairs defensive behaviours of zebrafish, which could be related to its action on brain cholinergic neurotransmission. Moreover, the use of the split depth tank could be an alternative strategy to assess group behaviour and depth preference after exposure to chemical compounds. © 2014 Elsevier Inc.


Kist L.W.,Grande Rio University | Rosemberg D.B.,Federal University of Rio Grande do Sul | Rosemberg D.B.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | Pereira T.C.B.,Grande Rio University | And 9 more authors.
Comparative Biochemistry and Physiology - C Toxicology and Pharmacology | Year: 2012

Microcystins (MCs) constitute a family of cyanobacterial toxins, with more than 80 variants. These toxins are able to induce hepatotoxicity in several organisms mainly through the inhibition of protein phosphatases PP1 and PP2A and oxidative stress generation. Since recent evidence shows that MCs can either accumulate in brain or alter behavior patterns of fish species, in this study we tested the in vitro and in vivo effects of MC-LR at different concentrations on acetylcholinesterase (AChE) activity in zebrafish brain. In vivo studies showed that 100 μg/L MC-LR led to a significant increase in the AChE activity (27%) when zebrafish were exposed to the toxin dissolved in water, but did not cause any significant changes when injected intraperitoneally. In addition, semiquantitative RT-PCR analysis demonstrated that 100 μg/L MC-LR exposure also increased ache mRNA levels in zebrafish brain. The in vitro assays did not reveal any significant changes in AChE activity. These findings provide the first evidence that brain AChE is another potential target for MCs and suggest that the observed increases in AChE enzymatic activity and in ache transcript levels after MC-LR exposure depend, at least partially, on branchial uptake or ingestion. © 2011 Elsevier Inc. All rights reserved.


Seibt K.J.,Grande Rio University | Seibt K.J.,Instituto Nacional Translacional em Medicina INCT TM | Da Luz Oliveira R.,Grande Rio University | Da Luz Oliveira R.,Instituto Nacional Translacional em Medicina INCT TM | And 8 more authors.
Journal of Neural Transmission | Year: 2012

Schizophrenia is a debilitating mental disorder with a global prevalence of 1% and its etiology remains poorly understood. In the current study we investigated the influence of antipsychotic drugs on the effects of MK-801 administration, which is a drug that mimics biochemical changes observed in schizophrenia, on Na+, K+-ATPase activity and some parameters of oxidative stress in zebrafish brain. Our results showed that MK-801 treatment significantly decreased Na+, K+-ATPase activity, and all antipsychotics tested prevented such effects. Acute MK-801 treatment did not alter reactive oxygen/nitrogen species by 2′7′- dichlorofluorscein (H2DCF) oxidation assay, but increased the levels of thiobarbituric acid reactive substances (TBARS), when compared with controls. Some antipsychotics such as sulpiride, olanzapine, and haloperidol prevented the increase of TBARS caused by MK-801. These findings indicate oxidative damage might be a mechanism involved in the decrease of Na+, K+- ATPase activity induced by MK-801. The parameters evaluated in this study had not yet been tested in this animal model using the MK-801, suggesting that zebrafish is an animal model that can contribute for providing information on potential treatments and disease characteristics. © Springer-Verlag 2012.


Ibrahim M.,Federal University of Rio Grande do Sul | Ibrahim M.,University of Peshawar | Mussulini B.H.M.,Federal University of Rio Grande do Sul | Moro L.,Federal University of Rio Grande do Sul | And 12 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2014

Anxiety-related disorders are frequently observed in the population. Because the available pharmacotherapies for anxiety can cause side effects, new anxiolytic compounds have been screened using behavioral tasks. For example, diphenyl diselenide (PhSe)2, a simple organoselenium compound with neuroprotective effects, has demonstrated anxiolytic effects in rodents. However, this compound has not yet been tested in a novelty-based paradigm in non-mammalian animal models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on the behavior of adult zebrafish under novelty-induced stress. The animals were pretreated with 0.1, 0.25, 0.5, and 1μM (PhSe)2 in the aquarium water for 30min. The fish were then exposed to a novel tank, and their behavior was quantified during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration-dependent manner. At 0.01 and 0.25μM, (PhSe)2 did not elicit effects on fish behavior. At 0.5μM, moderate behavioral side effects (e.g., lethargy and short episodic immobility) were noted. At the highest concentration tested (1μM), dramatic side effects were observed, such as burst behavior and longer periods of immobility. The results were confirmed by spatiotemporal analysis of each group. Occupancy plot data showed dispersed homebase formation in the 0.25μM (PhSe)2-treated group compared with the control group (treated with 0.04% DMSO). Furthermore, animals treated with 0.25μM (PhSe)2 showed a reduction in latency to enter the top and spent more time in the upper area of the tank. These data suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of anxiety evoked by novelty. © 2014 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 | Rico E.P.,Federal University of Rio Grande do Sul | Rico E.P.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | And 13 more authors.
PLoS ONE | Year: 2011

The open tank paradigm, also known as novel tank diving test, is a protocol used to evaluate the zebrafish behavior. Several characteristics have been described for this species, including scototaxis, which is the natural preference for dark environments in detriment of bright ones. However, there is no evidence regarding the influence of "natural stimuli" in zebrafish subjected to novelty-based paradigms. In this report, we evaluated the spatio-temporal exploratory activity of the short-fin zebrafish phenotype in the open tank after a short-period confinement into dark/bright environments. A total of 44 animals were individually confined during a 10-min single session into one of three environments: black-painted, white-painted, and transparent cylinders (dark, bright, and transparent groups). Fish were further subjected to the novel tank test and their exploratory profile was recorded during a 15-min trial. The results demonstrated that zebrafish increased their vertical exploratory activity during the first 6-min, where the bright group spent more time and travelled a higher distance in the top area. Interestingly, all behavioral parameters measured for the dark group were similar to the transparent one. These data were confirmed by automated analysis of track and occupancy plots and also demonstrated that zebrafish display a classical homebase formation in the bottom area of the tank. A detailed spatio-temporal study of zebrafish exploratory behavior and the construction of representative ethograms showed that the experimental groups presented significant differences in the first 3-min vs. last 3-min of test. Although the main factors involved in these behavioral responses still remain ambiguous and require further investigation, the current report describes an alternative methodological approach for assessing the zebrafish behavior after a forced exposure to different environments. Additionally, the analysis of ethologically-relevant patterns across time could be a potential phenotyping tool to evaluate the zebrafish exploratory profile in the open tank task. © 2011 Rosemberg et al.


Rosemberg D.B.,Federal University of Rio Grande do Sul | Rosemberg D.B.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | Braga M.M.,Federal University of Rio Grande do Sul | Braga M.M.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | And 16 more authors.
Neuropharmacology | Year: 2012

Taurine (TAU) is an amino sulfonic acid that plays protective roles against neurochemical impairments induced by ethanol (EtOH). Mounting evidence shows the applicability of zebrafish for evaluating locomotor parameters and anxiety-like behavioral phenotypes after EtOH exposure in a large scale manner. In this study, we assess the effects of TAU pretreatment on the behavior of zebrafish in the open tank after acute 1% EtOH (v/v) exposure (20 and 60 min of duration) and on brain alcohol contents. The exposure for 20 min exerted significant anxiolytic effects, which were prevented by 42, 150, and 400 mg/L TAU. Conversely, the 60-min condition induced depressant/sedative effects, in which the changes on vertical activity were associated to modifications on the exploratory profile. Although all TAU concentrations kept locomotor parameters at basal levels, 150 mg/L TAU, did not prevent the impairment on vertical activity of EtOH[60]. Despite the higher brain EtOH content detected in the 60-min exposure, 42, 150, and 400 mg/L TAU attenuated the increase of alcohol content in EtOH[60] group. In conclusion, our data suggest that both protocols of acute EtOH exposure induce significant changes in the spatio-temporal behavior of zebrafish and that TAU may exert a preventive role by antagonizing the effects induced by EtOH possibly due to its neuromodulatory role and also by decreasing brain EtOH levels. The hormetic dose-response of TAU on vertical exploration suggests a complex interaction between TAU and EtOH in the central nervous system. © 2012 Elsevier Ltd. All rights reserved.


Saute J.A.M.,Federal University of Rio Grande do Sul | Saute J.A.M.,Hospital Of Clinicas Of Porto Alegre Hcpa | Rieder C.R.M.,Federal University of Rio Grande do Sul | Rieder C.R.M.,Hospital Of Clinicas Of Porto Alegre Hcpa | And 24 more authors.
Journal of the Neurological Sciences | Year: 2015

Background In a recent phase 2 clinical trial in spinocerebellar ataxia type 3/Machado Joseph disease (SCA3/MJD), a neurogenetic disorder without specific therapy, benefits of lithium carbonate were found only on secondary efficacy outcomes, all related to ataxic features. In order to help designing future studies, we further analyzed the trial data searching for treatment response modifiers and metric properties of spinocerebellar ataxia (SCA) scales. Methods Efficacy analysis was performed with the Neurological Examination Score for the Assessment of Spinocerebellar Ataxia (NESSCA) and the Scale for the Assessment and Rating of Ataxia (SARA) subscores and with the subgroup of patients with independent gait according to the 8-meter walking-time (8MW). Interactions of clinical/molecular findings with treatment response, minimally important differences (MIDs), and sample size estimations for NESSCA, SARA, Spinocerebellar Ataxia Functional Index (SCAFI) and Composite Cerebellar Functional Score (CCFS) were evaluated. Results 62 SCA3/MJD patients had been randomly assigned (1:1) for the double-blind, placebo-controlled trial. While cerebellar NESSCA (range: 0-7 points) differed between groups 0.64 points (95% CI 0.23 to 1.05, p < 0.001) over the whole 48 weeks of study, favoring lithium, no effect was found on non-ataxia subscores. Among patients able to perform the 8MW on baseline, NESSCA (p = 0.010) and SCAFI (p = 0.015) differed between groups favoring lithium. Finally, estimated sample sizes for the scales were provided. Conclusion Lithium efficacy on cerebellar NESSCA, and on SCAFI and CCFS in the primary analysis, together with the lack of effect on non-ataxia features suggests that lithium should be tested in phase 3 trials in SCA3/MJD and that ataxia scales should be preferred to multisystem neurological instruments as the primary outcome. The inclusion of early stage patients is advisable in future clinical trials in SCA3/MJD. Trial registration clinicaltrials.gov identifier: NCT01096082. © 2015 Elsevier B.V.


Habekost C.T.,Federal University of Rio Grande do Sul | Habekost C.T.,Instituto Nacional Of Genetica Medica Populacional Inagemp | Schestatsky P.,Federal University of Rio Grande do Sul | Schestatsky P.,Hospital Of Clinicas Of Porto Alegre | And 16 more authors.
Orphanet Journal of Rare Diseases | Year: 2014

Background: Neurologic impairments in female heterozygotes for X-linked Adrenoleukodystrophy (X-ALD) are poorly understood. Our aims were to describe the neurological and neurophysiological manifestations of a cohort of X-ALD heterozygotes, and to correlate them with age, disease duration, mutations, X-inactivation and serum concentrations of a marker of neuronal damage, neuron-specific enolase (NSE). Methods. All 45 heterozygotes identified in our region, with previous VLCFA and molecular diagnosis, were invited to be evaluated through myelopathy scales JOA and SSPROM, nerve conduction studies and somatosensory evoked responses. X inactivation pattern was tested by HUMARA methylation assay. Serum NSE was measured by eletrochemiluminescense. Results: Thirty three heterozygote women were recruited: 29 (87%) were symptomatic. Symptomatic and asymptomatic women presented different m ± sd ages (43.9 ± 10.2 versus 24.3 ± 4.6), JOA (14.5 ± 1.7 versus 16.6 ± 0.2) and SSPROM (86.6 ± 7.9 versus 98.4 ± 1.1) scores (p < 0.05). Both JOA (r = -0.68) and SSPROM (r = -0.65) correlated with age, irrespectively of the disease status (p = 0.0001, Spearman). Delayed latencies in the central ascending conduction studies on the lower limbs were present in 72% of all heterozygotes, and correlated with SSPROM (r = -0.47, p = 0.018, Spearman). NSE values were higher in heterozygote than in control women (12.9 ± 7 and 7.2 ± 7 ng/ml, p = 0.012, Mann-Whitney U). Mutation severity and inactivation patterns were not associated with neurologic status. Conclusion: Neurologic manifestations, clearly related to age, were quite common in the present cohort. JOA and SSPROM scales were able to discriminate the asymptomatic from the symptomatic heterozygotes. Both scales might be useful tools to follow disease progression, in future studies. © 2014 Habekost et al.; licensee BioMed Central Ltd.


Braga M.M.,Federal University of Rio Grande do Sul | Braga M.M.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | Rosemberg D.B.,Federal University of Rio Grande do Sul | Rosemberg D.B.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | And 16 more authors.
Zebrafish | Year: 2013

Reactive zinc (Zn) is crucial for neuronal signaling and is largely distributed within presynaptic vesicles of some axon terminals of distinct vertebrates. However, the distribution of reactive Zn throughout the central nervous system (CNS) is not fully explored. We performed a topographical study of CNS structures containing reactive Zn in the adult zebrafish (Danio rerio). Slices of CNS from zebrafish were stained by Neo-Timm and/or cresyl violet. The Zn specificity of Neo-Timm was evaluated with Zn chelants, N,N,N′, N′-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), sodium diethyldithiocarbamate (DEDTC), Zn sulfide washing solution, and hydrochloric acid (HCl). Unfixed slices were also immersed in the fluorescent Zn probe (zinpyr-1). Yellow-to-brown-to-black granules were revealed by Neo-Timm in the zebrafish CNS. Telencephalon exhibited slightly stained regions, while rhombencephalic structures showed high levels of staining. Although stained granules were found on the cell bodies, rhombencephalic structures showed a neuropil staining profile. The TPEN produced a mild reduction in Neo-Timm staining, while HCl and mainly DEDTC abolished the staining, indicating a large Zn content. This result was also confirmed by the application of a Zn probe. The present topographical study revealed reactive Zn throughout the CNS in adult zebrafish that should be considered in future investigation of Zn in the brain on a larger scale. © Copyright 2013, Mary Ann Liebert, Inc.


Braga M.M.,Federal University of Rio Grande do Sul | Braga M.M.,Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao | Braga M.M.,Federal University of Santa Maria | Silva E.S.,Federal University of Rio Grande do Sul | And 17 more authors.
Toxicology Research | Year: 2015

The study of the effects of diethyldithiocarbamate (DEDTC) in some diseases has been in focus for many years. However, DEDTC is a metal chelator that can present neurotoxicity as side effect. Here we investigate the effect of DEDTC on the brain zinc (Zn) content and behavior. To address this issue we used adult zebrafish exposed to different concentrations of DEDTC. The animal's behavioral parameters were evaluated during exposure to DEDTC (0.2, 1, 5 mM in home tank water) for 1 h. At the end of the exposure period, the brain levels of DEDTC were measured. The analysis of the reactive Zn content in different regions of the brain and in glutamatergic neurons and radial glial cells was performed using histochemical and immunocytochemical techniques, respectively. We also measured the activity of a Zn-dependent enzyme, δ-aminolevulinate dehydratase (δ-ALA-D). We found that DEDTC exposure at 1 and 5 mM induced seizure-like behavior in the zebrafish and death at 5 mM. DEDTC in the zebrafish brain was detected with exposure to 1 and 5 mM (above 100 mg kg-1 tissue). The reactive Zn was reduced in glutamatergic neurons after 1 and 5 mM DEDTC exposure in radial glial cells. No changes in the brain δ-ALA-D activity were detected. Our results showed that DEDTC can accumulate in the brain, leading to impairment in neural behavior and in the homeostasis of reactive Zn in the brain. © 2015 The Royal Society of Chemistry.

Loading Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao collaborators
Loading Instituto Nacional Of Ciencia E Tecnologia Em Excitotoxicidade E Neuroprotecao collaborators