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1.
J Neuropathol Exp Neurol ; 82(9): 787-797, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37558387

RESUMO

Stroke is one of the principal cerebrovascular diseases in human populations and contributes to a majority of the functional impairments in the elderly. Recent discoveries have led to the inclusion of electroencephalography (EEG) in the complementary prognostic evaluation of patients. The present study describes the EEG, behavioral, and histological changes that occur following cerebral ischemia associated with treatment by G1, a potent and selective G protein-coupled estrogen receptor 1 (GPER1) agonist in a rat model. Treatment with G1 attenuated the neurological deficits induced by ischemic stroke from the second day onward, and reduced areas of infarction. Treatment with G1 also improved the total brainwave power, as well as the theta and alpha wave activity, specifically, and restored the delta band power to levels similar to those observed in the controls. Treatment with G1 also attenuated the peaks of harmful activity observed in the EEG indices. These improvements in brainwave activity indicate that GPER1 plays a fundamental role in the mediation of cerebral injury and in the behavioral outcome of ischemic brain injuries, which points to treatment with G1 as a potential pharmacological strategy for the therapy of stroke.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Ratos , Humanos , Animais , Idoso , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Infarto Cerebral
2.
Nutrients ; 15(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36904206

RESUMO

Ischemic stroke is one of the principal causes of morbidity and mortality around the world. The pathophysiological mechanisms that lead to the formation of the stroke lesions range from the bioenergetic failure of the cells and the intense production of reactive oxygen species to neuroinflammation. The fruit of the açaí palm, Euterpe oleracea Mart. (EO), is consumed by traditional populations in the Brazilian Amazon region, and it is known to have antioxidant and anti-inflammatory properties. We evaluated whether the clarified extract of EO was capable of reducing the area of lesion and promoting neuronal survival following ischemic stroke in rats. Animals submitted to ischemic stroke and treated with EO extract presented a significant improvement in their neurological deficit from the ninth day onward. We also observed a reduction in the extent of the cerebral injury and the preservation of the neurons of the cortical layers. Taken together, our findings indicate that treatment with EO extract in the acute phase following a stroke can trigger signaling pathways that culminate in neuronal survival and promote the partial recovery of neurological scores. However, further detailed studies of the intracellular signaling pathways are needed to better understand the mechanisms involved.


Assuntos
Lesões Encefálicas , Euterpe , AVC Isquêmico , Ratos , Animais , Extratos Vegetais/metabolismo , Antioxidantes/metabolismo , Frutas
3.
Front Neurol ; 12: 645138, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897602

RESUMO

The present study describes the electroencephalographic changes that occur during cerebral ischemia and reperfusion in animals submitted to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 30 min. For this, male Wistar rats were divided into two groups (n = 6 animals/group): (1) sham (control) group, and (2) ischemic/reperfusion group. The quantitative electroencephalography (qEEG) was recorded during the ischemic and immediate reperfusion (acute) phases, and then once a day for 7 days after the MCAO (subacute phase). The acute phase was characterized by a marked increase in the relative delta wave band power (p < 0.001), with a smaller, but significant increase in the relative alpha wave bandpower in the ischemic stroke phase, in comparison with the control group (p = 0.0054). In the immediate reperfusion phase, however, there was an increase in the theta, alpha, and beta waves bandpower (p < 0.001), but no alteration in the delta waves (p = 0.9984), in comparison with the control group. We also observed high values in the delta/theta ratio (DTR), the delta/alpha ratio (DAR), and the (delta+theta)/(alpha+beta) ratio (DTABR) indices during the ischemia (p < 0.05), with a major reduction in the reperfusion phase. In the subacute phase, the activity of all the waves was lower than that of the control group (p < 0.05), although the DTR, DAR, and DTABR indices remained relatively high. In conclusion, early and accurate identification of decreased delta wave bandpower, DTR, DAR, and DTABR indices, and an increase in the activity of other waves in the immediate reperfusion phase may represent an important advance for the recognition of the effectiveness of reperfusion therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31616380

RESUMO

Testosterone is responsible for several changes in the brain, including behavioral and emotional responses, memory, and cognition. Given this, we investigated changes in the brain wave profile caused by supplementation with exogenous testosterone in both castrated and non-castrated rats. We also investigated the serum testosterone levels, renal and hepatic function, and the lipid and behavioral profiles. We found changes in the spectral wave power in both groups (castrated and non-castrated animals) supplemented with exogenous testosterone, consistent with an aggressive/hostile profile. These changes were observed in the electrocorticographic evaluation associated with increased power in low-frequency (delta and theta) and high-frequency (beta and gamma) activity in the supplemented animals. The castrated animals presented a significant decrease of wave power in the alpha frequency. This correlated with a decrease of the performance of the animals in the elevated plus-maze evaluation, given that the alpha wave is linked to the execution and visualization of motor processes. In the behavioral evaluation, the castrated animals presented a reduced permanence time in the elevated-plus maze, although this was prevented by the supplementation of testosterone. Testosterone supplementation induced aggressive behavior in non-castrated animals, but not in castrated ones. Supplemented animals had significantly elevated serum testosterone levels, while their urea levels were significantly lower, but without clinical significance. Our data indicate that testosterone supplementation in non-castrated rats, but not in castrated ones, causes electrocorticographic changes that could be associated with more aggressive and hostile behavior, in addition to indicating a potential for personality disorder. However, further studies are required to elucidate the cellular and molecular changes caused by acute testosterone supplementation.

5.
Arq Neuropsiquiatr ; 77(2): 73-79, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30810589

RESUMO

Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.


Assuntos
Glucosilceramidase/genética , Mutação/genética , Doença de Parkinson/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Casos e Controles , Estudos Transversais , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco
6.
Arq. neuropsiquiatr ; 77(2): 73-79, Feb. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-983882

RESUMO

ABSTRACT Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.


RESUMO Mutações no gene GBA têm sido reportadas em pacientes com doença de Parkinson (DP) em diferentes países, incluindo o Brasil. Com o objetivo de confirmar esse padrão em uma amostra de pacientes com DP provenientes do Norte brasileiro, foi conduzindo esse estudo caso-controle investigando a frequência das duas mutações mais comuns do gene GBA (c.1226A>G; p.N370S e c.1448T>C; p.L444P) em um grupo de 81 pacientes com DP e 81 controles, usando PCR-RFLP e confirmado pelo sequenciamento direto de produtos de PCR. No grupo experimental, três pacientes (3,7%) foram heterozigotos para a mutação c.1226A>G; p.N370S e três (3,7%), para a mutação c.1448T>C; p.L444P Nenhuma das duas mutações foi detectada no grupo controle (p =0,0284). Pacientes com a mutação c.1448T>C; p.L444P demonstraram uma tendência a apresentar os sintomas mais precocemente, porém um número amostrai maior é necessário para confirmar essa observação. Nossos resultados sugerem uma associação entre essas duas mutações no gene GBA e o desenvolvimento de DP na população de pacientes do norte Brasileiro.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Parkinson/genética , Glucosilceramidase/genética , Mutação/genética , Polimorfismo de Fragmento de Restrição , Brasil , Estudos de Casos e Controles , Reação em Cadeia da Polimerase , Estudos Transversais , Fatores de Risco , Idade de Início , Estudos de Associação Genética
7.
Oral Maxillofac Surg ; 21(1): 21-26, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27873145

RESUMO

PURPOSE: Keratocystic odontogenic tumor (KCOT) is an aggressive benign tumor and the management by complete enucleation followed by cryotherapy maintains the inorganic bone matrix, resulting in better repair and reduces the rates of recurrence. A refrigerant spray with a propane/butane/isobutane gas mixture has been pointed to as an alternative to liquid nitrogen, because the device is easy to handle and contain within the cavity, providing better control and lower risk of injury to the adjacent soft tissue. Thus, the aim of this study was to evaluate the outcome of enucleation followed by cryosurgery using a refrigerant spray of this gas mixture in ten patients diagnosed with KCOT. METHOD: The biggest lesions received a prior treatment consisting of marsupialization to decrease the tumor size. During the surgeries, the lesions were removed by enucleation and the surgical site was sprayed with the gas mixture. RESULTS: Wound dehiscence was observed in all cases, which healed by the second intention. The mean follow-up period was 64.3 months (range 24-120 months). Eight of the ten patients showed no evidence of clinical or radiographic recurrence. Pathologic fractures and infections were not observed. CONCLUSIONS: The results obtained suggest that enucleation followed by cryosurgery is an effective therapy for managing KCOT.


Assuntos
Butanos/uso terapêutico , Criocirurgia/métodos , Neoplasias Mandibulares/cirurgia , Cistos Odontogênicos/cirurgia , Tumores Odontogênicos/cirurgia , Propano/uso terapêutico , Adolescente , Adulto , Aerossóis , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Ecotoxicol Environ Saf ; 132: 111-5, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27290641

RESUMO

Maintaining water quality within tolerable limits is a basic need of the riverside communities in the Amazon. Using endemic aquatic organisms as biological models is useful for monitoring the environment. In this study, potential cytotoxic and genotoxic damages in Plagioscion squamosissimus (commonly known as silver croaker) from the Marajó Archipelago were evaluated using a flow cytometry assay and a survey of micronuclei (MN) frequency as well as other nuclear abnormalities (NA). P. squamosissimus specimens were collected at four locations in the Marajó Archipelago. Blood samples from these fish were used in the flow cytometry assay and piscine micronucleus test, and the resulting data were analyzed using analysis of variance (ANOVA). We did not observe a difference in the erythrocyte cell cycle distribution among the samples (P=0.9992), which suggests the absence of cytotoxic agent-induced apoptosis. The piscine micronucleus test exhibited differences in the samples from São Sebastião da Boa Vista (SSBV), and those from Anajás produced the highest mutagenicity indices. The MN frequencies were low for all groups, but the groups exhibited significantly different frequencies (P=0.0033). Reniform nuclei, nuclei with extensions, and lobed nuclei were combined and considered NA. The frequency differences for these NA were significant among sampling sites (P <0.0001). This report is the first to use flow cytometry in fish to evaluate cytotoxic agent-induced apoptosis. The micronucleus test results indicate the presence of pollutants that can change the genetic material of the fish studied. We also demonstrate that the Amazonian fish P. squamosissimus is important not only as a comestible species but also as an adequate model for biomonitoring in aquatic environments.


Assuntos
Citotoxinas/toxicidade , Mutagênicos/toxicidade , Perciformes , Poluentes da Água/toxicidade , Animais , Apoptose/efeitos dos fármacos , Brasil , Ciclo Celular/efeitos dos fármacos , Dano ao DNA , Monitoramento Ambiental , Eritrócitos/efeitos dos fármacos , Testes para Micronúcleos , Perciformes/genética , Rios
9.
Molecules ; 20(10): 18777-88, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26501245

RESUMO

Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 µg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.


Assuntos
Antioxidantes/farmacologia , Meliaceae/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sobrevivência Celular , Células Cultivadas , Citoproteção , Avaliação Pré-Clínica de Medicamentos , Compostos de Metilmercúrio , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Cultura Primária de Células , Ratos Wistar
10.
Int J Environ Res Public Health ; 11(9): 9822-34, 2014 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25247425

RESUMO

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.


Assuntos
Poluentes Ambientais/toxicidade , Compostos de Metilmercúrio/toxicidade , Prolactina/farmacologia , Adulto , Células Cultivadas , Feminino , Células HL-60 , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Spec Care Dentist ; 34(3): 114-21, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24712505

RESUMO

The study aim was to explore the underlying dimensions of patients' perceptions and experiences of facial disfigurement following surgery for cancer treatment, using a qualitative approach based on individual in-depth interviews. Data analysis and interpretation consisted of separating responses into phrases or statements with a single thematic aspect. Subsequently, a number of dimensions and categories were created using a deductive-inductive content analysis. Three main categories emerged: discovering of the cancer, coping with the disease and disfigurement, and reconstructing a new identity. The initial stage elicited feelings of fear, denial, and guilt as a reaction to the stigma and prejudice. Coping strategies included resignation and acceptance, deepening religiosity, reinforcement of familiar cohesion, and creation of a social network of solidarity and support. The final stage comprised incorporation of the altered facial image, rehabilitation possibilities, reconstruction of personality and self-image, and the feeling of having overcome the disease. It was concluded that individual experiences are complex, challenging, and have striking effects on their lives. There is an urgent need for training and improvement in human resources to manage these patients in a multidisciplinary approach, aimed at their reintegration into society and reducing the prejudice and stigma of the disease and disfiguration.


Assuntos
Face , Neoplasias de Cabeça e Pescoço/cirurgia , Pacientes/psicologia , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
12.
J Neurosci Methods ; 198(1): 16-22, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21420432

RESUMO

Nitric oxide (NO) exerts important physiological and pathological roles in humans. The study of NO requires the immunolocalization of its synthesizing enzymes, neuronal, endothelial and inducible NO synthases (NOS). NOS are labile to formalin-fixation and paraffin-embedding, which are used to prepare human archival tissues. This lability has made NOS immunohistochemical studies difficult, and a detailed protocol is not yet available. We describe here a protocol for the immunolocalization of NOS isoforms in human archival cerebellum and non-nervous tissues, and in rat tissues and cultured cells. Neuronal NOS antigenicity in human archival and rat nervous tissue sections was microwave-retrieved in 50 mM Tris-HCl buffer, pH 9.5, for 20 min at 900 W. Neuronal NOS was expressed in stellate, basket, Purkinje and granule cells in human and rat cerebellum. Archival and frozen human cerebellar sections showed the same neuronal NOS staining pattern. Archival cerebellar sections not subjected to antigen retrieval stained weakly. Antigenicity of inducible NOS in human lung was best retrieved in 10 mM sodium citrate buffer, pH 6.0, for 15 min at 900 W. Inflammatory cells in a human lung tuberculoma were strongly stained by anti-inducible NOS antibody. Anti-endothelial NOS strongly stained kidney glomeruli. Cultured PC12 cells were strongly stained by anti-neuronal NOS without antigen retrieving. The present immunohistochemistry protocol is easy to perform, timeless, and suitable for the localization of NOS isoforms in nervous and non-nervous tissues, in human archival and rat tissues. It has been extensively used in our laboratory, and is also appropriate for other antigens.


Assuntos
Córtex Cerebelar/enzimologia , Óxido Nítrico Sintase/metabolismo , Isoformas de Proteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Arteríolas/enzimologia , Linhagem Celular , Pré-Escolar , Feminino , Feto , Granuloma/enzimologia , Granuloma/patologia , Humanos , Lactente , Recém-Nascido , Pulmão/citologia , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Ratos , Fatores de Tempo
13.
J. neurosci. methods ; 198(1): 16-22, 2011.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO | ID: biblio-1063957

RESUMO

Nitric oxide (NO) exerts important physiological and pathological roles in humans. The study of NO requires the immunolocalization of its synthesizing enzymes, neuronal, endothelial and inducible NO synthases (NOS). NOS are labile to formalin-fixation and paraffin-embedding, which are used to prepare human archival tissues. This lability has made NOS immunohistochemical studies difficult, and a detailed protocol is not yet available. We describe here a protocol for the immunolocalization of NOS isoforms in human archival cerebellum and non-nervous tissues, and in rat tissues and cultured cells. Neuronal NOS antigenicity in human archival and rat nervous tissue sections was microwave-retrieved in 50mM Tris–HCl buffer, pH 9.5, for 20 min at 900 W. Neuronal NOS was expressed in stellate, basket, Purkinje and granule cells in human and rat cerebellum. Archival and frozen human cerebellar sections showed the same neuronal NOS staining pattern. Archival cerebellar sections not subjected to antigen retrieval stained weakly. Antigenicity of inducible NOS in human lung was best retrieved in 10mMsodium citrate buffer,pH6.0, for 15 min at 900 W.Inflammatory cells in ahumanlung tuberculoma were strongly stained by anti-inducible NOS antibody. Anti-endothelial NOS strongly stained kidney glomeruli.Cultured PC12 cells were strongly stained by anti-neuronal NOS without antigen retrieving. The present immunohistochemistry protocol is easy to perform, timeless, and suitable for the localization of NOS isoforms in nervous and non-nervous tissues, in human archival and rat tissues. It has been extensively used in our laboratory, and is also appropriate for other antigens.


Assuntos
Ratos , Antígenos/imunologia , Pulmão/imunologia , Óxido Nítrico/análise , Óxido Nítrico/biossíntese , Óxido Nítrico/uso terapêutico , Cerebelo/imunologia , Imunoquímica/métodos , Sistema Nervoso , Técnicas de Cultura de Células/métodos
14.
Behav Brain Res ; 211(2): 191-7, 2010 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-20346984

RESUMO

Previous studies have shown that combined exposure to ethanol (EtOH) and methylmercury (MeHg) in rats during central nervous system development produces several behavioural impairments. This present study was done to investigate inhibitory avoidance acquisition and panic-like disorders in rats in an elevated T-maze (ETM) model of anxiety. Pregnant rats received tap water or EtOH at 22.5% (w/v) (6.5 g/kg per day, by gavage) during pregnancy and lactation. On the 15th day of pregnancy, half of each group received MeHg (8 mg/kg, by gavage). Adult offspring intoxicated by both EtOH + MeHg showed an increase in the ETM re-exposure time. Upon analysis of the enclosed arms latency in baseline and avoidance 1 session it was observed that the rats spent less time inside the arm, suggesting impairment in their short-term memory. The escape latency decreased for EtOH + MeHg and also for EtOH and MeHg groups, suggesting panic-like behaviour. After 24-h and 7-day trials (tests and retests), MeHg and EtOH + MeHg groups had their latency in the enclosed arm reduced with the exception of the EtOH group, revealing memory impairment. Upon analysis of the risk assessment, animals treated with EtOH + MeHg were the only ones to show a decrease in all evaluation stages. This study demonstrates that the exposure to both EtOH and MeHg has an impact on memory and panic-related behaviours, leading to the assertion that this association of toxicants should be studied more in detail to clarify the precise mechanisms of these pharmacological effects.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Etanol/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/embriologia , Depressores do Sistema Nervoso Central/toxicidade , Interações Medicamentosas , Poluentes Ambientais/toxicidade , Feminino , Masculino , Exposição Materna , Memória de Curto Prazo/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Teratogênicos/toxicidade
15.
Neurotoxicology ; 30(1): 23-30, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19100288

RESUMO

Studies involving alcohol and its interactions with other neurotoxicants represent the focus of several works of research due to the fact that the use of alcohol can sometimes leads to serious health problems. Fetal exposure to alcohol and mercury has a high incidence in some regions of Brazil, where there are pregnant women who are alcoholics and live in mining areas. This work was conducted to examine the effects of combined exposure to ethanol (EtOH) and methylmercury (MeHg) in rats during the development of the central nervous system (CNS). Experimental behavioral animal models/tests were used in order to examine locomotion, anxiety, depression and memory. Pregnant rats received tap water or EtOH 22.5% w/v (6.5 g/kg per day), by gavage) during pregnancy and breast-feeding. On the 15th day of pregnancy, some groups received 8 mg/kg of MeHg (by gavage). The groups were as follows: control, EtOH, MeHg and EtOH+MeHg. The experimental results showed that the EtOH, MeHg and EtOH+MeHg groups reduced the percentage of frequency and time spent in the open arms entries of the elevated plus-maze (EPM) test, when compared to the control group. This result suggests an anxiogenic behavioral response. The MeHg group increased locomotor activity in the arena and the immobility time in the forced swimming test, suggestive of depression-like behavior. The EtOH+MeHg group showed greater reductions in the percentages of frequency and time spent in the open arms entries in the EPM test, suggesting a sedative-behavior since the frequency of enclosed arm entries was affected. In the inhibitory avoidance task, the EtOH+MeHg group reduced the latency of the step-down response onto the grid floor, suggesting a cognitive and behavior dysfunctions. Taken together, the results suggest that EtOH and/or MeHg intoxication during the developing CNS may be a risk for deficits related to locomotor impairment, anxiety, depression and neurocognitive functions. There is a possibility that EtOH may prevent some of the MeHg responses, but the precise mechanism of action involved in this process needs to be considered for future research.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/embriologia , Etanol/toxicidade , Troca Materno-Fetal , Compostos de Metilmercúrio/toxicidade , Prenhez , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Interações Medicamentosas , Etanol/administração & dosagem , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Compostos de Metilmercúrio/administração & dosagem , Compostos de Metilmercúrio/análise , Atividade Motora/efeitos dos fármacos , Gravidez , Ratos , Natação
16.
Genet Mol Res ; 4(4): 822-31, 2005 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-16475130

RESUMO

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Inseticidas/toxicidade , Linfócitos/efeitos dos fármacos , Rotenona/toxicidade , Adulto , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Células Cultivadas , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Masculino , Índice Mitótico
17.
Neurosci Lett ; 343(1): 41-4, 2003 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-12749993

RESUMO

Acute exposure to ethanol has been shown to inhibit the function of N-methyl-D-aspartate (NMDA) receptors (NMDAR). However, the mechanism by which ethanol produces inhibition of NMDAR and the factors that modulate this effect are not completely understood. Nitric oxide (NO) is an important modulator of NMDAR function in the hippocampus. Therefore, we examined the effects of NO donors on the ethanol-induced inhibition of NMDAR. Primary cultures of hippocampal neurons were prepared from postnatal day 3 rats. After 7 days in culture, NMDAR currents were recorded by using whole-cell patch-clamp electrophysiological techniques. Effects of acute exposure to ethanol on these currents were assessed in the absence and presence of NO donors. We found that the NO donors 1-hydroxy-2-oxo-3-(N-ethyl-2-aminoethyl)-e-ethyl-1-triazene (NOC-12, 100 microM) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 500 microM) inhibit currents gated by 100 microM NMDA plus 0.5 microM glycine. The inhibitory effect of NOC-12 on NMDAR currents could not be observed when 100 microM of the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) was present. Importantly, it was found that ethanol inhibits NMDAR responses to a significantly lesser extent in the presence of these donors. Ethanol (65 mM) inhibited NMDAR responses by 42+/-2%. In the presence of NOC-12 or SNAP, ethanol inhibited NMDAR responses by 21+/-4% and 11+/-7%, respectively. The effect of NOC-12 on ethanol's actions on NMDAR currents was blocked by PTIO. Our results suggest that NO is a novel modulator of the acute effects of ethanol on NMDAR function.


Assuntos
Etanol/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Óxido Nítrico/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Células Cultivadas , Combinação de Medicamentos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos
18.
Nat Neurosci ; 5(1): 19-26, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11753414

RESUMO

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.


Assuntos
Exocitose/fisiologia , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Proteínas de Transporte Vesicular , Animais , Encéfalo/citologia , Encéfalo/embriologia , Encéfalo/metabolismo , Células Cultivadas , Derme/citologia , Derme/metabolismo , Diafragma/metabolismo , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário e Fetal , Imuno-Histoquímica , Técnicas In Vitro , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Proteínas do Tecido Nervoso/genética , Junção Neuromuscular/fisiologia , Neurônios/ultraestrutura , Técnicas de Patch-Clamp , Proteínas SNARE , Proteína 25 Associada a Sinaptossoma
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