Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2390

O Doutorado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).

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Acesso aberto (Open Access)
Análise do efeito tóxico e alterações transcriptomicas de células neuronais e gliais após exposição ao fluoreto
(Universidade Federal do Pará, 2019-05-23) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Corrêa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
Despite being widely used in dentistry for dental carie control, in high amounts fluoride may be associated with side effects of which the best known is dental fluorosis. In addition, studies suggest that even at low concentrations fluoride may exerts toxicity leading to damage on CNS. Functional toxicogenomics analysis of gene profile after exposure to contaminants has been used as a tool for the identification of biomarkers of exposure, as well as for the identification of signaling pathways that may be used for treatment and / or prevention of damage caused by the toxicity of certain compounds. As the molecular mechanism of fluoride toxicity still unknow, analysis of F chronic exposure on gene expression profile of CNS cells are necessary. Here we aimed to show the effect of fluoride exposure of plasma concentration founded on population that used to be exposed to fluoridated drink water, on the main CNS cells. In this way, we have used human cell lineage IMR-32 (neurons) and U87 (glial cells) to analyze parameter of viability, morphology and cell metabolism, ATP-synthesis, oxidative stress, DNA damage and global gene expression profile after 10 days exposure. Our results have shown that fluoride does not induce changes in IMR-32 cells. On the other hand, it induces cell death by necrosis, increased metabolism, decrease in ATP and GSH / GSSG in U87 cells and DNA fragmentation. The U87 gene expression profile is differentially altered after fluoride exposure, decreasing 1735 genes and an increasing expression of 1047 genes after exposure to 0.095μg / mL and decreasing of 1863 gene expression and increasing of 1023 expression after exposure to 0.22μg / mL. We also highlighted the major molecular pathways altered after exposure, such as the signaling pathway TNF-alpha via NFK-B and mitochondrial process. We also showed genes with significant importance biology (hub genes) such as the genes PTGES3, EP300, CYP1B1, RPS27A. Our results suggests that glial cell are affected by fluorides exposure and mitochondria has a major role on the mechanism of fluoride toxicity.
Acesso aberto (Open Access)
Atividade neuroprotetora do treinamento físico moderado contra os danos morfofuncionais cerebelares causados pelo consumo de etanol de forma intensa e episódica (Binge drinking) em ratos
(Universidade Federal do Pará, 2019-09) VIEIRA, Kátia Lamarão; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/0000-0003-1486-4013
Ethanol (EtOH) is a psychotropic drug, central nervous system (CNS) depressant, but widely encouraged and consumed by Brazilian society, as well as in much of the world, reflecting on a public health problem. In recent decades, teenagers have been practicing a very common practice, which is binge drinking. The harmful consumption of EtOH promotes, besides biopsychosocial alteration, the homeostatic imbalance that causes neurodegeneration and loss of function with motor disorders. In contrast, the practice of moderate physical training (MPT) has been recommended for the maintenance of physical and mental health, as well as prevention or minimization of the development of some diseases due to motor activity inducing plastic and dynamic changes in the CNS, in order to favor the neurogenesis, synaptogenesis and angiogenesis, besides contributing to the synaptic modulation. In view of the benefits of MPT, it was investigated the neuroprotective effects on motor, tissue and biochemical parameters in the cerebellum of rats exposed to binge-pattern EtOH from adolescence to adulthood. Forty male Wistar rats with 30 days old were used and divided into four groups, the control being sedentary animals and treated with distilled H2O; the trained, composed of animals exercised and treated with distilled H2O; EtOH, formed by sedentary animals and treated with doses of 3 g/kg/day EtOH, 20% (w/v); and Trained + EtOH, with exercised animals and treated with doses of 3 g/kg/day EtOH, 20% (w/v). The MPT protocol was performed on a rodent treadmill for 5 days for 4 weeks and binge-pattern EtOH doses were administered by intragastric gavage in the same weeks as the MPT. After this period, the animals were submitted to open field and beam walking behavioral tests. Then, they were euthanized for cerebellum collection, evaluating immunohistochemistry from the levels of trolox equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), nitrite and lipid peroxidation (LPO); as well as Purkinje cell morphology (PC), the fraction of anti-synaptophysine (SYP) and anti-myelin basic protein (MBP) immunolabeled area. According to the result, EtOH caused severe oxidative stress and motor damage, but the execution of the MPT performed promoted neuroprotective effects in the rat cerebellum, among them, the modulation of oxidative biochemistry by the restoration of GSH levels. decreased LPO levels and increased TEAC, as well as preventing neuronal loss, synaptic vesicle damage (SYP) and myelin components (MBP). Therefore, MPT can be considered as a significant therapeutic strategy for the acquisition of redox homeostasis, avoiding oxidative biochemistry imbalance, as well as tissue and functional damage in the cerebellum of rats treated by binge pattern EtOH.
Acesso aberto (Open Access)
Avaliação dos efeitos decorrentes da exposição ao cloreto de alumínio sobre parâmetros motores, cognitivos e de estresse oxidativo em ratos
(Universidade Federal do Pará, 2018-12-18) FERNANDES, Rafael Monteiro; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/6791765554367432
Aluminum (Al) is the third most abundant metal in the earth's crust, being present in large amounts in soil and water, its high bioavailability makes it an important environmental contaminant. Al is considered a neurotoxic agent and accumulates in the nervous system, being this behavior associated with several neurodegenerative diseases. However, little is known about its effects at doses similar to human consumption in the nervous and biochemical systems. Thus, this study investigated the effects of chronic exposure to aluminum chloride (AlCl3) on cognition, motor behavior and oxidative stress. For this, adult Wistar rats were divided into three groups: Al1 (8.3 mg / kg / day), Al2 (5.2 mg / kg / day) and Control (Distilled water) being exposed orally for 60 days. After the exposure period, behavioral, histological, oxidative stress parameters and quantification of aluminum levels in the blood were performed. There were no changes in motor behavior, there was change in only one exploratory parameter and in cognition. No differences were found in the population of the purkinje neurons between the experimental groups. Exposure to Al increased levels of this metal in the blood, also altering the parameters of oxidative biochemistry. Thus, we can affirm that exposure to Al in rats, at doses equivalent to urban exposure and in potentially safe doses are capable of promoting breakage of blood homeostasis, altering hippocampal biochemical balance, generating a state of oxidative stress and cognitive damage, not being able to promote significant changes in the cerebellum and motor parameters.
Acesso aberto (Open Access)
Caracterização da injúria no córtex motor de ratos em um modelo de exposição crônica ao metilmercúrio (MeHg)
(Universidade Federal do Pará, 2016-12-21) SANTANA, Luana de Nazaré da Silva; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
The mercury is an environmental contaminant which poses a great risk to human health. Exposure to this toxic metal occurs mainly through a diet contaminated by methylmercury (MeHg) in low concentrations and over a long period of time. Thus, in this study we propose an assessment of the effects of MeHg on the motor cortex in an animal model of chronic exposure and low dose, similar to dietary exposure in areas of high environmental toxicity of mercury. Adult rats were exposed to MeHg for 60 days with a dose of 0.04 mg/kg/day, while the control group received only the vehicle. After this period, they were subjected to behavioral testing in order to evaluate the motor performance after mercury exposure, and then sacrificed and evaluated for oxidative biochemical parameters (change in the concentration of nitrite - NO Lipid Peroxidation - LPO and Antioxidant Capacity Total) as well as evaluation of total deposits of mercury in the motor cortex and changes in cell density of neurons and astrocytes. Data were tabulated and statistically analyzed by Student's t-test (p <0.05). It was possible to observe total mercury deposits in the motor cortex, and deficits in motor parameters, with a reduction in the overall locomotion, on balance and increase in the number of failure, coupled with a significant increase in the levels of NO and LPO and decreased ability antioxidant full of animals exposed, reducing the population of astrocytes and neurons compared to control animals these findings suggest that exposure of adult animals to MeHg, even at low dose and chronically, causes changes in the motor cortex with damage to their functions.
Acesso aberto (Open Access)
Efeitos do exercício físico sore parâmetros cognitivos e bioquímicos em ratos expostos ao etanol de forma intensa e episódica (Binge Drinking)
(Universidade Federal do Pará, 2018-12-21) TEMBRA, Dinair Pamplona dos Santos; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
The consumption pattern of heavy and episodic ethanol, weekend consumption, characterizes the pattern of excessive alcohol consumption or binge drinking that promotes an imbalance of brain metabolic functions, contributing to neurodegeneration and cerebral dysfunction. And because it is a legal drug, it has global relevance in public and social health. In this way, we aimed to investigate the effects of physical training of moderate intensity, in treadmill, on the deleterious effects of ethanol on hippocampus functions related to memory and learning. For this, 80 Wistar rats were divided into four groups: Control group; Trained group (animals trained and treated with distilled water); Ethanol group (animals not trained and treated with doses of 3 g / kg / day of ethanol, 20% w / v); and ethanol + trained group (animals trained and exposed to ethanol). Physical exercise was performed on a treadmill for 5 days a week for 4 weeks and all doses of ethanol and distilled water were administered by intragastric gavage (three days a week) in four repeated cycles. After the experimental period, the animals were submitted to the task of object recognition and Morris aquatic labyrinth test, and after euthanasia, blood and hippocampus were collected to measure levels of antioxidant capacity equivalent to trolox (TEAC), content of reduced glutathione (GSH), nitrite and lipid peroxidation. (LPO). Our results showed that EtOH caused marked oxidative stress and mnemonic damage, and physical exercise promoted neuroprotective effects, including modulation of oxidative plasma biochemistry (by restoration of GSH levels) and hippocampus (reducing levels of LPO and increasing antioxidant parameters) and improving cognitive function. Therefore, physical exercise may be an important prophylactic and therapeutic tool to improve and even prevent the deleterious effects of ethanol on cognitive functions.
Acesso aberto (Open Access)
Exposição subcrônica de ratos wistar jovens a dose baixa de chumbo induz déficits locomotores e alterações morfológicas associados a estresse oxidativo e disfunção sináptica
(Universidade Federal do Pará, 2018-12-18) PENHA, Luana Ketlen Reis Leão da; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3219037174956649
Lead (PB) is a heavy metal, which can be utilized in the production of several compounds. The main route of human exposure is through the consumption of contaminated food or water, and once absorbed, about 99% of the circulating lead spreads to soft tissues, teeth, bones and brain. In the Central nervous system (CNS), several studies have demonstrated deficits in learning capacity, cognition and intellectual development in humans exposed to lead during a given period of life. However, it is poorly understood the mechanisms of action involved with the toxicity of Pb. From this, this study aimed to evaluate the exploratory, motor and tissue effects induced by the subchronic exposure of young wistar rats to 50 mg/Kg of lead, associated with possible mechanisms of action. Male Wistar rats were exposed for 55 days at a dose of 50mg/Kg of Pb per gavage, and the control animals received distilled water. The open field, inclined plane and route-rod tests were performed for locomotor evaluation. Staining was performed with Hematoxylin and Eosin, as well as immunohistochemistry for the quantification of mature neurons, myelin sheath and synaptic vesicles. To evaluate the protein expression, the Proteomic profile was performed. The statistical analysis was performed by Student's T-Test, being considered significant p < 0.05. After we observed lead deposition only in the cerebellum, it was possible to characterize exploratory and motor deficits in the rats exposed to lead, and we observed a decrease in the number of Purkinje cells, as well as mature neurons, reduction of vesicles synaptic and decreased myelin sheath. In the evaluation of oxidative stress induction, it was possible to evaluate the increase of MDA and nitrite only in the motor cortex. And in the evaluation of protein expression, both regions presented alterations in proteins responsible for the release process of neurotransmitters, as well as receptors and second messengers, and also proteins involved in the process of apoptose. Thus, we conclude that the subchronic exposure to low Pb dose of young Wistar rats promoted locomotor and histological tracings, associated with induction of oxidative stress, alterations in the process of cell signaling, as well as death by apoptosis.

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