Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2375

O Mestrado 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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Agora exibindo 1 - 5 de 5

Acesso aberto (Open Access)
Alterações de expressão gênica na linhagem de glioblastoma humano U87 após exposição ao MeHg e HgCl2
(Universidade Federal do Pará, 2016-12-02) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
The organic and inorganic forms of mercury have been pointed as important contaminants in several world regions due to its toxicological characteristics. Various studies have reported that the intoxication by methylmercury (MeHg) and mercury chloride (HgCl2) can lead to central nervous system impairment. It is generally agreed that glial cells are important for the mechanisms responsible for cellular protection against the damages caused by the mercury. However, little is known about the influence of the mercury in the cells genome. Hence, in the present study we did a complete mapping of the humam glial cells genetic network after mercury exposition with the aim to indentify the possible genetic alterations that occurred via the organic and inorganic forms of mercury. Our results demonstrated that U87 lineage cells are more sensitive to MeHg exposition when compared with HgCl2 exposition. Using an analysis of the concentration curves the LC50 was obtained from 28.8μM and 10,68μM after 4h and 24h exposition to MeHg and a LC50 of 92.25μM and 62.75μM after the same time periods exposition to HgCl2. Regarding the genic pool, our results have shown that both metal forms led to alterations in the genic dosage where the MeHg exposition was highly influenced by the concentration and time, whereas the HgCl2 exposition seemed have been strongly influenced by the exposition time. In total there were 205 indentified genes with a lower genic dosage and 188 genes with elevated expression, (Fold change > 5) after 4h exposition and 5μM of MeHg, and 204 down-regulated genes; and 180 up-regulated genes after HgCl2 exposition in the same concentration. The analysis after 24h exposition showed 90 down-regulated genes and 3 up-regulated genes after 1μM of MeHg; 116 genes were down-regulated and 66 genes were up-regulated after a 10μM exposition of MeHg. As for the HgCl2, there were 98 down-regulated genes and 73 up-regulated genes for the groups exposed to 5μM of HgCl2; 326 down-regulated genes and 66 up-regulated genes for the groups exposed to 62,75μM of HgCl2. Our dataset suggests that both mercurial forms are able to alter the cell genetic expression profile thus interfering in important signaling paths prone to gives rise to biochemical impairments and glial cells phenotypes.
Acesso aberto (Open Access)
Avaliação neurocomportamental da exposição crônica ao Mercúrio inorgânico na memória social e memória emocional de ratos wistar machos adultos
(Universidade Federal do Pará, 2015-02-20) FERNANDES, Rafael Monteiro; SILVA, Márcia Cristina Freitas da; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
Inorganic mercury is easily absorbed by ingestion or cutaneous. However, a relatively small amount of Hg2 + crosses the blood brain barrier or biological membranes, and in adult rats, the retrograde axonal transport only way to Hg2+ uptake by neurons, presenting great potential neurotoxic. The aim of this study was to determine the effects of chronic exposure to mercury chloride in social and emotional memory in adult rats. For this we used male Wistar rats (n= 40) with 5 months of age , divided into two groups , one of which was exposed to mercury chloride (HgCl2) by intragastric gavage (0,375mg / kg) for 45 days. The other group, called the control group (n=20) received distilled water by gavage. The following behavioral tests were used: the open field test, social recognition test for the evaluation of social memory; the elevate T maze test (LTE) was used to assess learning in the state of avoidance and short and long - term memories. After completion of the tests, the animals were sacrificed to evaluate the level of total mercury in the hippocampus by an Atomic Absorption Spectrophotometer. The results showed that animals subjected to exposure to mercury chloride did not show deficits in exploration activity. The data from social recognition test, showed that there was no change in social memory. In LTE test, the group exposed to HgCl2 required a greater number of exposures for the acquisition of avoidance criteria (p<0.05) and a higher latency in the open apparatus arm (p<0.05). After 24 hours, it was found that treated animals spent less time in the closed arms than in the control group, suggesting the long-term memory deficits. By just watching the HgCl2 group, noticed an improvement in the retest, indicating preservation in the short-term memory. The data of atomic absorption spectrometry showed greater deposition of mercury in the hippocampus of affected animals, as compared to control animals.
Acesso aberto (Open Access)
Caracterização das alterações no córtex motor de ratos adultos submetidos à exposição crônica com mercúrio inorgânico
(Universidade Federal do Pará, 2016-12-12) TEIXEIRA, Francisco Bruno; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
Mercury is a highly toxic heavy metal, which can be found in organic and inorganic elemental forms in the environment. The inorganic mercury has lower liposolubility and consequently, lower absorption in the body, and lower passage through the blood brain barrier. For this reason, exposure models using inorganic mercury in rats to evaluate its effects in the central nervous system are rare, mainly in adults. Therefore, we investigate the potential of low concentration of mercury chloride (HgCl2), in a chronic exposure model to promote motor changes associated to variables in the oxidative balance, cellular cytotoxicity and apoptosis in the motor cortex of adult rats. For this purpose, rats were exposed for 45 days to a dose of 0.375 mg/kg/day. After this period, the animals were submitted to motor evaluation and then were collected for measurement of total deposited mercury in neural parenquima, assessment and quantification of cellular cytotoxicity and apoptosis and evaluation of the oxidative balance. Furthermore, animals were perfused to evaluate the density of mature neurons and astrocytes of the motor cortex. It was observed that chronic exposure to inorganic mercury decreased balance and fine motor coordination. In addition, we found that this exposition model led to cytotoxicity and cell death by apoptosis, formation of deposits of mercury and oxidative stress evidenced by the increase of lipoperoxidation and the concentration of nitrites and decrease in total antioxidant capacity. Thus, our results provide evidence that a exposition to inorganic mercury, even before his lower capacity to cross the biology barriers, It is still capable to inducing motor changes associated to cell death and apoptosis and oxidative stress in the motor cortex of the adult rats.
Acesso aberto (Open Access)
Exposição subcrônica ao metilmercúrio induz danos teciduais, bioquímicos e proteômicos em cerebelos de ratos
(Universidade Federal do Pará, 2018-07-04) MATTA, Pedro Philipe Moreira; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
Methylmercury (MeHg) represents the most toxic form of mercury, which in chronic intoxications induces motor and cognitive impairment in adult rats. Studies suggest that this metal has a tropistic effect on the cerebellum, however few researches aim to elucidate the mechanisms associated with low-dose MeHg-induced damage in a subchronic exposure model. Thus, the objective of this study was to verify motor, tissue, oxidative and proteomic biochemical alterations induced by subchronic exposure to low doses of MeHg. Fifty six male Wistar rats, 90 days old, were divided into two groups: control group (distilled water) and exposed group (0.04 mg / kg / day of MeHg), both administered via intragastric gavage for 60 days. After the exposure period, the open field and rotarod behavioral tests were performed. Subsequently, the cerebellum from these animals were collected for biochemical analysis, proteomics, mercury tissue deposits, and immunohistochemistry evaluation. Statistical analysis was performed using the Student's t-test, considering a significant value of p <0.05. The proteomic profile was analyzed by the ProteinLynx Global SERVER ™ software (PLGS). Proteins with p <0.05 were considered super-regulated proteins and those with p <0.95 were considered as sub-regulated proteins. The test used was Fisher's exact test with Bonferroni correction. Our results demonstrated a decrease in the motor tests of the animals exposed to MeHg. Open field test showed a decrease in total distance covered and the number of rearing in comparison to the control group with p <0.05. Rotarod test presented a decrease in the time for the first latency to fall and an increase in the number of falls in the MeHg group in comparison to the control with p <0.05. The biochemical evaluation showed an increase in nitrite and lipid peroxidation levels and a reductions of Antioxidant Capacity Against Peroxils radicals (ACAP) with p <0.05. Considering the proteomic profile of these animals, among the 1220 proteins identified, 436 proteins were found exclusively in the control group and 311 proteins exclusively in the MeHg group. Also, 358 proteins were found overexpressed and 115 subexpressed proteins. All proteins interactions were depicted on 3 interactions networks to perform proteomic alterations analysis. In addition, the tissue evaluation showed a decrease in Purkinje cells and NeuN + cells and a smaller amount of IBA1+ cells. Area fraction analysis showed a smaller number of GFAP positive cells, synaptophysins and MBP +. Thus, our results suggest that MeHg intoxication provoked cellular and proteomic damage probably related to induced oxidative stress and also reflecting on motor deficit in behavioral tests.
Acesso aberto (Open Access)
Investigação dos efeitos bioquímicos, proteômicos e estruturais da exposição prolongada ao cloreto de mercúrio sobre a medula espinhal de ratos
(Universidade Federal do Pará, 2019-09) CORRÊA, Márcio Gonçalves; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/0000-0003-1486-4013
Mercury chloride (HgCl2) is a pollutant widely found in the environment. This form of mercury is able to promote several damages to the Central Nervous System (CNS), including changes to the motor cortex, an area related to the planning and execution of motor activity. However, the effects of HgCl2 on the spinal cord, an important pathway for the communication between the CNS and the periphery, are still unknown. We exposed adult rats for 45 days to HgCl2, orally, to investigate the effects on oxidative biochemistry, proteomic profile, and spinal cord structures. Our results showed that exposure to this metal promoted increased levels of Hg in the medullary parenchyma, impaired oxidative biochemistry, changes in antioxidant system proteins, energy metabolism and myelin structure; as well as caused disruption in the myelin sheath and reduction in neuronal density. Thus, we conclude that prolonged exposure to HgCl2 triggers biochemical changes and in the expression of several proteins, resulting in damage to the myelin sheath and reduction of neurons in the spinal cord, which may be related to motor damage. Keywords:

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