Navegando por Assunto "Sistema nervoso"

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Acesso aberto (Open Access)
Ação da ciclosporina A na via de ativação do fator de crescimento de nervo (NGF) em células neurais do SNP
(Universidade Federal do Pará, 2016-08-26) JESUS, Jessica Batista de; SENA, Chubert Bernardo Castro de; http://lattes.cnpq.br/8620752020290438; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
A is an immunosuppressive drug with known action on T cells of the immune system used in organ transplantation and autoimmune diseases. In the nervous system, cyclosporin A acts by inhibiting the action of Calcineurin, an important second messenger from pathway of signal transduction Nerve Growth Factor (NGF), resulting in hyperphosphorylation of the nuclear factor of activated T cells (NFAT), and downregulation of NGF, TrkA and other factors that participating in this pathway. The NFAT1-4 family are dependent isoforms of calcineurin, while NFAT5 isoform is independent. It has been demonstrated the neuroprotective role of Cyclosporin A via calcineurin dependent or independent. In this study, we evaluate the action of Cyclosporine A in the PNS system, that could be associated with levels of NGF, TrkA and an independent of calcineurin transcription factor (NFAT5) that interplay the plasticity of neuronal cells derived from Dorsal root ganglia (DRG) maintained in cultures. We use E10 DRG cultures supplemented with medium conditioned E9 Retinal treated with Cyclosporin A for 48 and 72 hours. Cultures enriched neurons were confirmed by calcium imaging method. The action of Cyclosporine A in the neuritogenesis was assessed by bright field microscopy, expression of NGF, TrkA and NFAT5 was performed by RT-PCR, intracellular accumulation of NGF was evaluated by immunofluorescence and the presence of TrkA in neurons. The viability test of the cultures treated or not with the concentrations of 1-40μM Cyclosporine A was performed by MTT method. The results show an increase of NGF levels in mixed cultures, and TrkA receptor and NFAT5 in cultures enriched in neurons following treatment with cyclosporine A. Given the importance of NGF pathway in the development and maintenance of the SNP, the use of Cyclosporin A have activity in the peripheral nervous system cells, which might be used in the clinic with new target for new therapies.
Acesso aberto (Open Access)
Análises dos genes TP53, PTEN, IDH1 e IDH2 em tumores não gliais do sistema nervoso humano
(Universidade Federal do Pará, 2016-06-17) LOPES, Cleiton Mendes; ANSELMO, Nilson Praia; http://lattes.cnpq.br/6518287721873199
Despite the considerable incidence, studies of genetic changes in gene TP53, PTEN, IDH2 and IDH1, in not glial tumors are rare and, in some cases, nonexistent. Glial tumors are usually not classified as benign and rarely evolve to malignancy, with different classifications, effects and locations. The tumor suppressor genes and response to DNA damage, TP53 and PTEN are among the most commonly mutated gene in human tumors. The genes IDH1 and IDH2 are involved in cell metabolism and also were frequently found mutated in gliomas, melanomas and leukemias, currently being considered as good markers for gliomas. Genetic analyzes were performed in those genes, in order to verify that are associated with the etiology and/or progression of non-glial tumors of Human Nervous System (HNS). SSCPPCR techniques for the amplification of the region of interest and mutational screening of samples for subsequent sequencing were used. We analyzed 37 samples of non-glial tumors (14 schwannomas, meningiomas 3, 4 Medulloblastomas, 2 neurocytomas and 14 metastases of Central Nervous System (CNS). Only the gene IDH1 polymorphisms presented on the SSCP 12 (32.4%) samples, and then subjected to sequencing. However, sequencing reactions were satisfactory in only 5 samples, of the polymorphic, (1 metastasis, meningioma 1 and 3 schwannomas). Analysis of these samples have identified 5 different mutations, one present in all, one transversion T → A in codon 106 of exon 4 of the IDH1 gene resulting in amino acid substitution of threonine by serine. Were also identified other mutations in noncoding regions (intron 4) of gene IDH1 in two of these samples. The mutations found in our study had not yet been reported in the literature. Our results indicate the participation the gene IDH1 in the pathogenesis of these tumors.
Acesso aberto (Open Access)
Envelhecimento e doenças neurodegenerativas crônicas na Amazônia brasileira: implantação de novas metodologias de avaliação em pacientes com declínio cognitivo leve e doença de Alzheimer
(Universidade Federal do Pará, 2011-09-27) SOUZA, Aline Cristine Passos de; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286; SÓSTHENES, Márcia Consentino Kronka; http://lattes.cnpq.br/7881527576747420
By 2025, the number of elderly people in the world will double and by 2050 will reach around two billion individuals, with the majority of them in developing countries. Alzheimer's disease (AD) is the fourth disease that most compromises the quality of life in elderly. This work aims to suggest new methodologies for evaluating elderly people with mild cognitive impairment and Alzheimer‟s disease, introducing a Brazilian version of the TSM-"Test Your Memory" and showing the performance fo this people in tests from CANTAB. It is an analytical, retrospective, longitudinal case-control study, performed at the Laboratory of Neurodegeneration and Infection, University Hospital João de Barros Barreto, from January 2009 to January 2011. Ninety five individuals 65 years old or older were divided in three groups: Alzheimer's disease (AD, n = 21), mild cognitive impairment (DCL, n = 31) and control (n = 43). Patients with previous stroke, primary depression, head injury, other dementias and other neuropsychiatric disorders, and serious visuo-auditory deficits were excluded. The participants were submitted to an initial assessment, screening with GDS-5 and DSM-IV, the International Physical Activity Questionnaire (IPAQ), CERAD neuropsychological test battery and the TSM - Test Your Memory (Brazilian version).Statistical analysis was performed using one-way ANOVA, defining the p-value<0.05 to detect significant differences. Female individuals of mixed ethnicity, aged 70 to 79 years predominated in all groups. The average MMSE score between the three groups was significantly different (control: 26.6± 2.2; DCL: 25.1 ± 2.6, DA: 17.3 ± 4.9, p <0.05), however, the TSM proved to be a more sensitive test to distinguish DCL patients from AD (control: 42.4± 5; DCL: 35.5 ± 7.7, DA: 25.7 ± 8, p <0.01 ). The three groups had different mean scores. In the CERAD word list, clock test, TNBr and phonological verbal fluency. The performance in TSM was significantly lower in DCL and AD groups than in the control group. And DA group was worse in this test than the DCL group too. The tests and measurements of CANTAB that best separate the three groups from the performance obtained were RVP A‟, PAL-trials to success and PAL-total errors in 6 patterns phase. Good correlations were found between the TSM and other tests, especially with the MMSE (Pearson‟s coefficient r = 0.79, p <0.0001) and clock test (r = 0.76, p <0.0001), as well as good correlations between the measures of PAL and TSM and MMSE. Physical activity level, in the control group was higher than in all other groups. When the level of physical activity and performance on cognitive tests were correlated, there were no significant differences in the different groups, except by a better performance in word recall test from CERAD, and word list in DCL group (DCL "active":4.7 ± 1.8; DCL"not active": 3 ± 1.5,p <0.01). Taken as a Whole, these results suggest that the application of automated automated neuropsychological tests associated with routine clinical tests and TYM, improve the clinical assessment´s sensitivity and reliability, especially in the early stages of dementia where the precoceous and accurate diagnosis are essential to guide therapeutic actions, drugs or behavioral modifications.
Acesso aberto (Open Access)
Intoxicação experimental por Tetrapterys multiglandulosa (Malpighiaceae) em ovinos
(2005-06) CORREA, Gabriela Riet; TERRA, Fabiano Fonseca; SCHILD, Ana Lucia; CORREA, Franklin Riet; BARROS, Severo Sales de
Cardiac fibrosis was observed in a calf showing dullness, weakening and respiratory insufficiency in a farm in the state of São Paulo, where cardiac insufficiency, abortion and nervous signs in cattle were associated with the ingestion of Tetrapterys multiglandulosa. The objectives of this paper were to determine the susceptibility of sheep to the intoxication by T. multiglandulosa, to describe the clinical and pathological characteristics of the intoxication, and to evaluate the possibility of using sheep as an experimental species for toxicological studies with this plant. In a previous experiment to determine the toxicity of T. multiglandulosa to be used in sheep, the green plant was given to a steer at the dose of 22g per kg body weight (g/kg/bw), daily, during 9 days. After 9 days the steer showed nervous signs, and on the 12thday was euthanatized. No gross lesions were observed at necropsy. Status spongiosus was observed on the deeper layers of the cerebral cortex and subcortical white matter. Six male sheep were divided in three groups of two sheep each. Group 1 (Sheep 1 and 2) received daily doses of 6 g/kg/bw of the dry plant, during 30 days; Group 2 (Sheep 3 and 4) received daily doses of 3 g/kg/bw, during 60 days; and Group 3 was the control group. Sheep 1 was euthanatized 30 days after the start of the ingestion. Only cardiac arrhythmia was observed clinically, and no lesions were observed at necropsy. Sheep 2, 3 and 4 had also cardiac arrhythmia from day 9, 12 and 18, respectively. From day 52 they started to show depression, reluctance to move and incoordination. Clinical signs got gradually worst and the sheep were euthanatized on days 60, 70 and 80, when clinical signs were marked, and the animals will die at any moment. Hydrothorax, hydropericardium, ascites, nutmeg appearance of the liver and hard whitish myocardium, mainly in the interventricular septum and left ventricle, were observed at necropsy. Histologically, the heart of Sheep 2, 3 and 4 had areas of fibrosis associated with mononuclear cell infiltration. No lesions were found in the heart of Sheep 1. The 4 treated sheep had status spongiosus in different areas of the cerebrum and brain stem, mainly of the deep layers of the cerebral cortex and subcortical white matter. Status spongiosus were also observed in the cerebellar white matter and cervical medulla. In the later the vacuolization was moderate in the white matter and mild in the grey matter. Status spongiosus were mild in Sheep 1 and moderate to severe in Sheep 2, 3 and 4. On electron microscopy it was observed that the status spongiosus is due to an intramyelinic edema. No gross or histologic lesions were observed on the two control sheep, which were euthanized on day 80 after the start of the experiment.
Acesso aberto (Open Access)
Intoxicação por Ipomoea carnea subsp. fistulosa (Convolvulaceae) em caprinos na Ilha do Marajó, Pará
(2009-07) OLIVEIRA JÚNIOR, Carlos Alberto de; BARBOSA NETO, José Diomedes; DUARTE, Marcos Dutra; CERQUEIRA, Valíria Duarte; CORREA, Franklin Riet; TORTELLI, Fábio Py; RIVERO, Gabriela Riet Correa
Ipomoea carnea subsp. fistulosa is a swainsonine-containing plant causing a glycoprotein storage diseases in ruminants, mainly in goats in northeastern Brazil. Seven farms were visited on the Marajo Island, state of Pará, northern Brazil, six in the municipality of Cachoeira do Arari and one in the municipality of Soure. In all farms native pastures had shortage of forage and were largely invaded by I. carnea subsp. fistulosa. On the three farms goats presented difficulties in standing, ataxia, hypermetria, wide-based stance, lateral gait, intention tremors, spastic paresis or weakness, abnormal postural reactions, nystagmus, loss of equilibrium and falling to the side or backward. On two farms the prevalence was of 32% (23/71) and 100% (32/32). On another farm one goat out of 19 had severe clinical signs, but the others of the flock were not examined clinically. Cattle, sheep and buffaloes were not affected. Six goats were euthanized and necropsied. No gross lesions were observed. Upon histological examination the main lesion was the vacuolization of the perikaryon of neurons and cytoplasm of epithelial cells of thyroid, liver, kidney, pancreas and macrophages of different organs. In the central nervous system the vacuolization of the perikaria was more severe in Purkinje cells of the cerebellum and in nuclei of the brain stem, mainly the cerebellar nuclei. Wallerian degeneration of axons and gliosis was also observed. The high frequency of the disease on the three farms suggests that poisoning by I. carnea subsp. fistulosa is very important for goats on Marajó Island where there are large amounts of the plant in the pastures.
Acesso aberto (Open Access)
Modelo de doença de parkinson em camundongos baseado na injeção unilateral 6-hidroxidopamina no estriado: caracterização do curso temporal das alterações comportamentais e da degeneração nigroestriatal
(Universidade Federal do Pará, 2008-07-03) CARDOSO, Váldina Solimar Lopes; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306
Parkinson‘s disease (PD) is a common neurodegenerative disease that affects mainly elderly people. It is characterized by the progressive cell death of dopaminergic neurons in the nigrostriatal system, which causes the development of the classic tetrad of symptoms: resting tremor, muscular rigidity, bradikynesia and postural instability. There is evidence that both genetic and environmental factors play a role in the development of the disease. In order to better understand the mechanisms undelying this disease, several animal models have been used to mimic some aspect of the dopaminergic degeneration. The intracerebral injection of 6-OHDA has been one of the most used PD model. This toxin is preferentially injected into the striatum or in the substantia nigra to provoke a selective degeneration of dopaminergic neurons from the nigrostriatal pathway. When a unilateral injection is used, the animals display a stereotypical rotational behavior after pharmacological induction, and such behavior has been largely used as a measure of the degree of nigroestriatal degeneration. This model is well characterized in rats and has been an useful tool to test neuroprotective therapies. Mice, as much as rats, are also largely used in studies of DP, but the 6-OHDA model has not been well described. The objective of the present work was to improve the characterization of the hemiparkinsonism model based on a single unilateral intraestriatal injection of 6-OHDA in C57BL6 mice, to provide a more detailed evaluation of the temporal course of the neuronal dopaminergic degeneration in the substantia nigra and to establish the degree of correlation between the degeneration and behavioral changes. Our results showed that a single injection of 10 μg of 6-OHDA into the striatum causes progressive degeneration of nigral dopaminergic neurons dependent of survival time, and that there is a high correlation between the rate of degeneration and the rotational behavior induced by apomorphine. Spontaneous motor behaviors such as ambulation and rearing had a lower correlation with the degeneration. Therefore, we suggest that the rotational behavior induced by apomorphine provides a good measure of the degree of asymmetry in the nigrostriatal pathway of mice with 6- OHDA-induced hemiparkinsonism and that it can indeed be an useful tool in experiments to test therapies with neuroprotective potential for Parkinson’s disease.