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Dissertação Acesso aberto (Open Access) Avaliar a influência do tratamento crônico com vitamina C em um modelo de estresse provocado pela dor inflamatória induzida por ácido acético em ratos wistar adolescentes(Universidade Federal do Pará, 2018-12-21) NASCIMENTO, Gisely da Silva; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806Stress in adolescence may be linked to consequences that may persist throughout life. The injuries suffered in the brain, due to exposure to stress factors, contribute to the development of pathologies related to behavior and emotionality, such as anxiety and depression. These two pathologies have been taking on increasingly frightening proportions these days, especially among adolescents and young people, due to brain plasticity in this phase. Therefore, the aim of this study was to evaluate the influence of chronic vitamin C treatment on stress in adolescent animals in a model of inflammatory pain induced by acetic acid. Using the open field test, vitamin C was shown to significantly reduce anxiety-related behavior. This chronic treatment also satisfactorily reversed memory and learning deficits in Morris water maze. In conclusion, the chronic treatment with vitamin C has beneficial effects on the emotionality and behaviors of adolescent animals submitted to acetic acid injections. In addition, the acetic acid injection model has been shown to be efficient in inducing an anxious state of the animals.Tese Acesso aberto (Open Access) Efeitos anti-inflamatórios e neuroprotetores do extrato de gergelim preto (Sesamum indicum L.) em um modelo experimental de isquemia estrial(Universidade Federal do Pará, 2024-03) SANTOS, Ijair Rogério Costa dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072Acidente Vascular Encefálico (AVE) é uma neuropatologia caracterizada como o surgimento súbito global ou focal de déficits da função neurológica de duração superior a 24 horas ou que leve a morte, cuja única causa reside na origem vascular. Estudos sobre a incidência, comprometimento físico e mortalidade enquadram o AVE como a segunda causa de morte no mundo e a principal complicação orgânica que leva às disfunções físico-neurológicas, frequentemente, graves e permanentes. A indução do AVE em animais de experimentação e o entendimento de sua fisiopatologia, bem como a busca de tratamentos que minimizem os danos neurológicos e estimulem a recuperação morfofuncional do indivíduo afetado são temas de grande relevância científica e clínica. Neste estudo, investigamos os possíveis efeitos neuroprotetores e/ou anti-inflamatórios do extrato supercrítico de gergelim preto (Sesamun indicum L.) após lesão isquêmica focal por microinjeções de 80 pmol de endotelina-1 no estriado de ratos adultos, usando as coordenadasestereotáxicas: 1,2 mm, anterior-posterior; 2,5 mm, médio-lateral; 4,0 mm, dorsoventral. Após a indução do AVE, os grupos controles foram tratados com tween a 5% e os tratados receberam 150 mg/kg de gergelim, ambos, por via intraperitoneal, em duas doses diárias de 75 mg/kg. A neuropatologia foi obtida em secções encefálicas com 50 e 20 μm de espessuras e coradas com violeta de cresila, para identificar a área de lesão, e/ou imunomarcadas por anticorpos específicos à identificação de neurônios (anti-NeuN), astrócitos (anti-GFAP) e micróglia (anti-ED1). Secções de 5 μm de espessura de rim e fígado corados por métodos histológicos e histoquímicos não mostraram alterações morfológicas nas células que compõem esses órgãos essenciais, sugerindo baixa toxicidade do extrato. Todas as secções coradas e/ou imunomarcadas foram visualizadas em microscópio óptico e seuscampos mais ilustrativos, em todos os tempos de sobrevida e grupos experimentais,foram capturados digitalmente e editados em computador. A quantificação das célulasNeuN+(neurônios), micróglia/macrófagos (ED1+) e astrócitos (GFAP+) na área de lesão, três secções por lâmina, todo campo ao redor de lesão por secção, com auxílio de uma gradícula de área 0,0625 mm2 na ocular possibilitou o teste t-Student à análise estatística entre os grupos e o uso do programa Microsoft Excel à plotagem dos gráficos. Por fim, uma caracterização da citotoxicidade in vitro, bem como a verificação do índice de acidez do extrato revelou baixa acidez e mínima agressividade em células sanguíneas, que ratifica o uso do extrato supercrítico em estudos que visem otratamento de doenças agudas e crônicas no SNC.Dissertação Acesso aberto (Open Access) Efeitos neurocomportamentais e no estresse oxidativo em ratos tratados com extrato etanólico de própolis amarela(Universidade Federal do Pará, 2015) SILVEIRA, Cinthia Cristina Sousa de Menezes da; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101Propolis is a resinous substance produced by bees that collect raw material from different parts of plants, through the addition of salivary secretions and wax. In Brazil, 13 types of propolis were chemically characterized. In the yellow propolis of Mato Grosso do Sul were identified 15 compounds, all belonging to the class of triterpenoids, and low levels of phenolic compounds and flavonoids. This work aims to conduct behavioral and biochemical assays with acute administration of yellow propolis ethanolic extract. 8 groups of male Wistar rats, 3 months, were used (n = 10 per group) and were divided into control (Tween 5%), positive control for anxiolytic activity (diazepam), positive control for antidepressant activity (fluoxetine), positive control for mnemonic effect (caffeine), 4 doses of the extract (1, 3, 10, 30mg/kg). The extract administration was performed acutely, intraperitoneally. Behavioral tests were open field, elevated plus maze, forced swimming and inhibitory avoidance. After the behavioral testing was performed to collect blood in the intracardiac area of the animals for determination of nitric oxide, malondialdehyde, catalase, superoxide dismutase and total antioxidant capacity. The results obtained in the open field test showed spontaneous locomotion preserved and anxiolytic-like activity, confirmed result with the elevated plus maze. In the forced swimming test, the yellow propolis ethanolic extract demonstrated action of antidepressant-like. In the inhibitory avoidance test showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase and superoxide dismutase, induced by stress. With these results it is concluded that the yellow propolis ethanolic extract has anxiolytic, antidepressant, mnemonic and antioxidant activity.Dissertação Acesso aberto (Open Access) Efeitos neuroprotetores e anti-inflamatórios do óleo de copaíba (Copaifera reticulata Ducke) em ratos adultos submetidos a isquemia do córtex motor por microinfecções de Edotelina-1(Universidade Federal do Pará, 2019-02-15) SILVA, Paulo Rodrigo Oliveira da; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072Stroke is a neural disorder caused by interruption of blood flow in vessels that irrigate the brain (ischemic stroke) or rupture of these (hemorrhagic stroke), causing cognitive, sensory and / or motor deficits. With the exception of thrombolytic use, which has a very narrow therapeutic window and is little used, there are no other pharmacological treatments or cellular therapy available for this pathological condition. Thus, it is necessary to search for new treatments, such as the development of neuroprotective agents. The Amazon is a rich source of natural products, but its therapeutic actions for diseases of the central nervous system (CNS) have been little investigated. In this work, we have investigated the neuroprotective and anti-inflammatory actions of copaiba oil-resin (COR). Adult Wistar rats were submitted to focal ischemia by microinjections (80pMol/μl) of endothelin-1 (ET-1) directly into the motor cortex and were treated with daily doses of COR (400mg / kg) or 5% tween. The animals were perfused at 7 days after the injury. The histopathological analysis was performed by Nissl staining (brain) and hematoxylin-eosin (liver and kidneys). Immunohistochemistry was performed for labeling of neurons (anti-NeuN), astrocytes (anti-S100) and caspase (anti-caspase-3). Morphometry showed a reduction in the lesion size area (copaiba-treated animals (15.96 ± 1.53 mm2); control animals (28.82 ± 2.65 mm2). Histopathological examination of the liver and kidneys did not find changes indicative of toxicity. In the quantitative analysis, neuronal preservation was observed, but no statistical difference was noticed between the groups regarding astrocytes analysis (S100+ cells). The COR-treated group showed an increase in caspase-3 expression. It is concluded that COR may play a neuroprotective role, contributing to neuronal survival in the area of ischemic penumbra, but future work is needed to find out the mechanisms underlying this phenomenon.Tese Acesso aberto (Open Access) Estudo exploratório de alterações na linguagem em pacientes com Alzheimer em indivíduos com baixa escolaridade(Universidade Federal do Pará, 2014-03-21) LIEBENTRITT, Edilene Maia; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286The present report describes features of the language, especially some of the discursive aspects of healthy elderly or with mild cognitive decline or with mild or moderate Alzheimer's disease. A total of 44 elderly were evaluated, including 22 healthy, 4 with mild cognitive decline, 9 with mild Alzheimer disease and 9 with moderate Alzheimer's disease, classified by the CDR criteria. Mini-mental state examination, the short version of Boston naming, verbal fluency and narrative tests by visual confrontation (based on the oral description of picture cookie theft) were applied. Performances were estimated on the selected tests and the oral narratives were classified and assessed using Groves - Wright criteria. Parametric statistical tests were applied and the level of significant statistical differences was set at p<0.05. An inventory and analysis of the lexicon and grammatical categories from the oral narratives were performed using Z scores. To that end the STABLEX software was applied. As compared with mild cognitive decline it was found that semantic verbal fluency is better in the healthy elderly. The narratives showed statistically significant differences between healthy elderly and mild cognitive impairment in the analysis of frequency of use of vocabulary and grammatical categories as a whole, and statistically significant differences between healthy and all other groups in the analysis of each grammatical category. The analysis of the vocabulary and grammatical categories allowed to identify impairments of narrative function as measured by the type of vocabulary and preferred or rejected grammatical categories. The results contribute to distinguish the characteristics of the narrative of healthy elderly, elderly with mild cognitive decline or with mild or moderate Alzheimer's disease, pointing out early changes in language aspects that may possibly be used to evaluate the progression of the disease.Tese Acesso aberto (Open Access) Papel da serotonina no comportamento defensivo do paulistinha (Danio rerio Hamilton 1822) adulto: Diferenças entre modelos comportamentais, linhagens, e efeitos do estresse predatório agudo(Universidade Federal do Pará, 2014-11-14) OLIVEIRA, Caio Maximino de; HERCULANO, Anderson ManoelAnxiety disorders present the highest incidence in the world population among psychiatric disorders, and the clinical efficacy of anxiolytic drugs is low, partially due to lack of knowledge on the neurochemical bases of these disorders. To reach a more ample and evolutionarily grounded comprehension of these phenomena, the use of phylogenetically older species can be an interesting approach in the field of behavioral modeling; thus, we suggest the use of zebrafish (Danio rerio Hamilton 1822) in the attempt to understand the modulation of these behaviors by the serotonergic system. We demonstrate that extracellular serotonin levels in the brains of adult zebrafish exposed to the light/dark preference test [LDT] (but not to the novel tank test [NTT]) are increased in relation to animals which are handled, but not exposed to the apparatuses. Moreover, serotonin tissue levels levels in the hindbrain and forebrain are elevated by the exposure to the LDT, while tissue levels in the midbrain are elevated by exposure to the NTT. Extracellular serotonin levels correlate positively with scototaxis, thigmotaxis and risk assessment in the LDT and negatively with geotaxis in the NTT. Acute treatment with a low dose of fluoxetine (2.5 mg/kg) increases scototaxis, thigmotaxis, and risk assessment in the LDT, and decreases geotaxis and freezing and facilitates habituation in the NTT. Treatment with buspirone decreases scototaxis, thigmotaxis and freezing at 25 and 50 mg/kg in the LDT and decreases risk assessment at 50 mg/kg; in the NTT, both doses decrease geotaxis, while the highest dose decreases freezing and facilitates habituation. Treatment with WAY 100635 decreases scototaxis at 0.003 and 0.03 mg/kg, while only the highest dose decreases thigmotaxis and risk assessment in the LDT. In the NTT, both doses decrease geotaxis, while only the lower dose facilitates habituation and increases homebase time. Treatment with SB 224289 did not alter scototaxis, but increased risk assessment at 2.5 mg/kg; in the NTT, this drug decreased geotaxis and decreased erratic swimming at 2.5 and 5 mg/kg, while at 2.5 mg/kg it increased homebase time. Treatment with DL-para-clorophenylalanine (2 x 300 mg/kg injections, separated by 24 h) decreased scototaxis, thigmotaxis and risk assessment in the LDT, and increased geotaxis and homebase time and decreased habituation in the NTT. When animals were pre-exposed to a conspecific “alarm substance”, extracellular serotonin levels were raised in association with an increase in scototaxis, freezing and erratic swimming in the LDT; both behavioral and neurochemical effects were blocked by pre-treatment with fluoxetine (2,5 mg/kg), but not with WAY 100,635 (0,003 mg/kg). Animals from the leopard strain show increased scototaxis and risk assessment in the LDT, as well as increased 5-HT tissue levels in the encephalon; the behavioral phenotype is rescued by treatment with fluoxetine (5 mg/kg). These data suggest that the serotonergic system of zebrafish modulates behavior in the LDT and NTT in opposite ways; that the fright response produced by alarm substance seems to increase serotonergic activity, an effect which is possibly mediated by serotonin transporters; and that at least one high-anxiety mutant phenotype is associated with serotonin uptake. It is thus suggested that from a functional point of view serotonin increases anxiety and decreases fear in zebrafish.Dissertação Acesso aberto (Open Access) Potencial neuroprotetor da atividade física em populações ribeirinhas da Amazônia expostas ao mercúrio(Universidade Federal do Pará, 2025-05) NAZARÉ, Caio Gustavo Leal de; OLIVEIRA, Marcus Augusto de; http://lattes.cnpq.br/6036530007649294; HTTPS://ORCID.ORG/0000-0002-4772-9929; LOPEZ, Maria Elena Crespo; http://lattes.cnpq.br/9900144256348265; https://orcid.org/0000-0002-1335-6853Mercury is a highly toxic metal and is among the three substances with the greatest potential threat to human health. Its organic form, methylmercury, is particularly dangerous to human health due to its ability to easily cross biological barriers. The brain is a critical target for methylmercury, where it can cause neurological disorders, including motor, visual, auditory, behavioral, and cognitive deficits. Glial cells are closely involved in the mechanisms mediating such disorders and can either protect or damage the central nervous system (CNS), depending on the context. Moreover, no pharmacological treatment has proven effective against mercury intoxication to date, and literature has shown that both physical exercise and physical activity are capable of modulating glial aspects involved in the pathophysiology common to various neurological conditions and methylmercury intoxication. Thus, a potentially therapeutic and non-pharmacological approach, such as physical exercise – and even physical activity – would be particularly suitable for vulnerable populations who are economically, socially, and geographically disadvantaged, such as the riverine communities of the Amazon, who are chronically exposed to methylmercury through the consumption of contaminated fish. This study aims to assess whether physical activity profiles can influence the symptomatology of methylmercury intoxication in riverside residents of the Tucuruí Lake region. Interviews were conducted to obtain a profile of physical activity and self-reported neurological symptoms, and total mercury was measured from hair samples. Our results point to a possible and complex relationship between hair mercury levels and physical activity, suggesting that physical exercise may be a viable alternative to be included in daily life.Tese Acesso aberto (Open Access) Sensibilização dependente de tempo em paulistinhas adultos como modelo de transtorno de estresse pós-traumático: papel do óxido nítrico(Universidade Federal do Pará, 2015-08-11) LIMA, Monica Gomes; OLIVEIRA, Caio Maximino de; http://lattes.cnpq.br/7758963790962240; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247Post-traumatic stress disorder (PTSD) is classified as a trauma- and stressor-related disorder, a set of severely debilitating neuropsychiatric disorders characterized by the disregulation of stress responses after a traumatic event. Zebrafish (Danio rerio Hamilton 1822) emerged as an important model organism for the study of genetic, neuropharmacological and behavioral functions, such as the study of anxiety and stress. Nitric oxide (NO) is a gaseous transmitter that appears to have an important role in the regulation of neurobehavioral responses to stresss, including in zebrafish. In this scenario, we propose a behavioral model for PTSD in the evaluation of the time-dependent sensitization of behavior in zebrafish as a consequence of the exposure to conspecific alarm substance (AS) – a potent stressor. Using this model, we will verify the role of the nitrergic system in this process of sensitization. Animals will be exposed to AS and kept stress-free for 24 h; after this interval, animals' behavior will be analyzed. 5 experiments will be made to investigate: i) the delayed effect of alarm substance on different behavioral tasks in zebrafish, ii) a comparison of time-dependent sensitization on shortfin and longfin phenotypes; a comparação da sensibilização dependente de tempo nas linhagens shortfin e longfin, iii) the application of Behavioral Cutoff Criteria on timedependent sensitization, iv) the quantification of extracellular glutamate and tissue nitrite in the telencephalon after exposure to alarm substance, and v) the participation of NO on the initiation and consolidation of time-dependent sensitization. Our results revealed that: i) alarm substancce produces a delayed sensitization of anxiety (increased geotaxis, decreased habituation, increased erratic swimming and thrashing in the novel tank test; decreased time on white, increased erratic swimming, risk assessment and thigmotaxis on the ligh/dark test) and arousal (increased swim distance on the first trial and increased habituation slope in the startle reactivity test). ii) In relation to shortfin animals, exposure of longfin zebrafish to AS sensitized time on white, risk assessment and thigmotaxis more, while shortfin animals had more erratic swimming. Iii) 25.74% of AS-exposed animals reached criteria for Extreme Behavioral Response (EBR), and 20% reached criteria for Minimal Behavioral Response VII (MBR); in non-exposed animals, only 4% reached criteria for EBR and 96% reached criteria for MBR. Animals classified as EBR spent less time in the white compartment, with shorter entries, more thigmotaxis and more erratic swimming than animals classified as MBR and non-exposed controls. iv) treatment with L-NAME 30 minutes before AS exposure did not block the behavioral sensitization in the light/dark test; v) treatment with L-NAME 30 minutes after AS exposure blocked the sensitization of scototaxis and risk assessment; vi) treatment with L-NAME 90 minutes after AS exposure blocked the sensitization of risk assessment, erratic swimming and thigmotaxis. Theses results suggest that time dependent sensitization is a good model to study PTSD and point to NO as a important mediator in this process.
