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)
Alteração diferencial nos astrócitos radiais do hipocampo e neurogênese em aves marinhas com rotas migratórias constantes
(Universidade Federal do Pará, 2019-08-17) LIMA, Camila Mendes de; MAGALHÃES, Nara Gyzely de Morais; http://lattes.cnpq.br/2519507561210918; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286; https://orcid.org/0000-0001-6611-6880
Little is known about environmental influences on radial glia–like α cells (radial astrocytes) and their relation to neurogenesis. Because radial glia is involved in adult neurogenesis and astrogenesis, we investigated this association in two migratory shorebird species that complete their autumnal migration using contrasting strategies. Before their flights to South America, the birds stop over at the Bay of Fundy in Canada. From there, the semipalmated sandpiper (Calidris pusilla) crosses the Atlantic Ocean in a non-stop 5-day flight, whereas the semipalmated plover (Charadrius semipalmatus) flies primarily overland with stopovers for rest and feeding. Using hierarchical cluster and discriminant analysis of morphometric features to classify three-dimensionally (3D) reconstructed cells, we identified two morphotypes of radial glia, designated as Type I and Type II. The migratory process affected these cells differentially, with more intense morphological changes in Type I than in Type II morphotypes in both species. We also compared the number of doublecortin (DCX)-immunolabeled neurons with morphometric features of radial glial–like α cells in the hippocampal V region between C. pusilla and C. semipalmatus before and after autumn migration. Compared with migrating birds, the convex hull surface of radial glial–like α cells of wintering birds significantly increased in both C. semipalmatus and C. pusilla. This increase correlated with an increase of the total number of DCX-immunolabeled neurons in wintering birds. The decreased radial astrocyte morphological complexity in the semipalmated sandpiper and its increase in the semipalmated plover, a species that probably relies more on visuospatial information for navigation, may be significant, despite phylogenetic and other differences between these taxa. The migratory flight of the semipalmated plover, with stopovers for feeding and rest, versus the non-stop flight of the semipalmated sandpiper may differentially affect radial astrocyte morphology and neurogenesis.
Acesso aberto (Open Access)
Análise comparativa dos padrões neurodegenerativos da substância cinzenta em diferentes áreas corticais de ratos adultos submetidos à lesão isquêmica focal
(Universidade Federal do Pará, 2012-09-27) SANTOS, Enio Maurício Nery dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke can occur in any region of the central nervous system (CNS). The cerebral cortex is one of the most often affected areaby this acute neural disorder, but there are no studies that have compared the damaging pattern in different cortical regions after acomparable focal ischemia. The aim of this investigation was to evaluate the degenerative pattern of different cortical areas after focal ischemic injury. Focal ischemia was induced by stereotaxic microinjections of endothelin-1 (ET-1) into the somatosensory, motor and association cortices of adult rats (N = 45). The control animals were injected with the same volume of sterile saline (N = 27). The animals were perfused 1, 3 and 7 days after the ischemic event. The brain was removed, postfixed, cryoprotected, and sectioned in a cryostat. The general histopathology was evaluated in 50μm sections stained with cresyl violet. 20μm sections were submitted to immunohistochemistry for astrocytes (anti-GFAP), activated microglia / macrophages (anti-ED1) and overall microglial population (anti-Iba1). The damaging patterns werequalitatively evaluated under optical microscopy and quantitatively by counting the number of cells in the ipsilateral and contralateral sides to injury.Descriptive statistics and comparisons within and between groups were performed using analysis of variance with Tukey post-hoc test. Conspicuous ischemic tissue loss, microglial activation and astrocytosis were observed mainly 3 and 7 days after ischemia, which was not observed in control animals. The tissue loss and activation of glial cells were more intense in the somatosensory cortex, followed by the motor cortex. The association cortex displayed less damage compared to other cortical areas, which was confirmed by quantitative analysis. The results suggest that an ischemic lesion of the same intensity induces a differential pattern of tissue loss and neuroinflammation, depending on the cortical area, and that the primary sensory and motor areas are more susceptible to ischemia than association areas.
Acesso aberto (Open Access)
Atividade antiproliferativa e antineoplásica de flavonóides da espécie Brosimum acutifolium em modelo de glioblastoma in vitro
(Universidade Federal do Pará, 2013-05-24) MAUÉS, Luis Antônio Loureiro; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Among the tumors that affect the nervous system, glioblastoma multiforme (GBM) is notable by its high degree of aggressiveness and poor prognosis, with an average survival of 15 months from diagnosis. The present study aimed to investigate the antiproliferative and antineoplastic activity of four flavonoids isolated from species Brosimum acutifolium (Huber). two flavans: 4'-hydroxy-7,8-(2",2"-dimethylpyran)-flavan (BAS-1) and 7,4'-dihydroxy-8-(3,3-dimethylallyl)-flavan (BAS-4), and two chalcones: 4,2'-dihydroxy-3',4'-(2",2"-dimetilpirano)-chalcone (BAS-6) and 4,2',4'-trihydroxy-3'-(3,3-dimethylallyl)-chalcone (BAS-7), tested on rat C6 glioblastoma in vitro. Our results showed good cytotoxic activity for flavans (BAS-1, -4) and the chalcone BAS-7, with IC50 less than 100 μM in the MTT viability test, since the chalcone BAS-6, showed no cytotoxicity at the concentrations tested. These flavonoids showed less cytotoxity for non-neoplastic cell (glia), with higher degree of security for the BAS and BAS-4-7, once showed lower cytotoxic effect on non-neoplastic cell, and less hemolytic. Analysis of cell migration showed that treatment with BAS-1; -4 and -7 at low concentrations was effective in promoting the inhibition of cell migration. These three flavonoids were also very promising in inhibiting colony formation and growth, and promote cell cycle arrest with a substantial increase in population SubG0 for treatment with BAS-1 and -4 with 100 μM. The flavans BAS-1 and -4 also showed increased ability to promote losing in the integrity of the mitochondrial membrane potential (ΔΨm) and increased for staining with Annexin V, indicating that these drugs cause death by apoptosis. However the analysis by electron microscopy showed markedly the presence of autophagic vacuoles in the treatment with BAS-4 suggesting that the process of cell death occurs by apoptosis as well as autophagy. Based on these results it can be concluded that the flavonoids BAS-1, -4, and -7 have potential as an anticancer agent in the therapy of GBM and BAS-4 is the most promising of all.
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)
Caracterização dos efeitos comportamentais, teciduais e bioquímicos da administração intermitente e episódica de EtOH em ratas da adolescência à fase adulta
(Universidade Federal do Pará, 2016-10-18) FERNANDES, Luanna de Melo Pereira; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
The consumption of ethanol (EtOH) is enhanced particularly in adolescent female pubic. The EtOH intake and intermittent episodic own consumption rate around 3 times per week. The toxic effects of this kind of consumption is especially dangerous over the continuous consumption of EtOH followed due to the high dietary intakes of abstinence, causing major changes in the central nervous system (CNS) maturing in a short time consumption. Considering the epidemiological relevance and the harmful effects of EtOH on the oxidative balance, hormone production and neurotrophin CNS maturing, the aim of this study was to investigate the behavioural, tissue and biochemical responses derived from intermittent and episodic consumption of EtOH in rats in phase from adolescence to adulthood. Wistar female adolescents (n = 80) received by gavage, distilled water or EtOH (3 g/kg/day) for 3 consecutive days per week. The animals were assessed seven and a half hours after the last administration day 1, 4 and 8 weeks of episodes of binge drinking (37, 58 and 86 DPN, respectively), besides, a period of 14 days of abstinence was added after BD 8 (100 DPN) to evaluate the ability to reverse the CNS damage generated on it. The battery of behavioural tests consisted of spontaneous locomotor activity, object recognition, elevated plus maze, test pole, walking beam and rotarod. The animals were sacrificed and blood samples collected for evaluation of corticosterone levels of malondialdehyde, catalase activity, the activity of superoxide dismutase and glutathione content. Therefore, the hippocampus was dissected to quantify the immunocontent BDNF. The administration of EtOH reached average peak blood concentration of 197.4 mg / dL and the period of 7.5 hours after the last administration EtOH in acute binge blood concentration was 0.7 mg / dL. Thus, the animals underwent behavioural tests post-consumer EtOH, not under the drug effect. Consumption of EtOH in binge did not affect weight gain of adolescent animals into adulthood, however, reduced the exploratory locomotor activity, impaired motor coordination, balance and motor learning associated with bradykinesia, as well as loss in the mnemonic process and increased anxiety-like behaviour. These losses were accompanied by hormonal elevation of corticosterone, reduced hippocampal BDNF levels and systemic imbalance in the oxidative balance. Thus, it was possible to identify that the damage found on the similar behaviour to anxiety, short-term memory, bradykinesia and spontaneous locomotor activity appeared from EtOH post-consumption for three consecutive days, however, they showed no recovery or worsening of damage after repeated episodes. In contrast, there was recovery of short-term memory in object recognition task associated with the return of normal levels of BDNF in adulthood. Moreover, it showed worsening in motor learning in young adult phase followed by gradual and partial recovery after prolonged period of drug withdrawal, yet the loss of motor coordination and balance remained in adulthood.
Acesso aberto (Open Access)
Desenvolvimento de aplicativo para realização do finger tapping test e a influência do sexo e da dominância manual no desempenho do finger tapping test baseado em smartphone
(Universidade Federal do Pará, 2023-11) BRITO, Felipe André da Costa; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; https://orcid.org/0000-0002-4525-3971
The Finger Tapping Test (FTT) is a classical neuropsychological test that assesses motor functioning, and recently it has been employed using smartphones. For classical protocols, it has been observed that sex and handedness influence the performance during the test. By assessing the influence of sex and handedness on the test, it is possible to adjust the performance measurements to ensure the validity of test results and avoid sex- and handedness-related bias. The present study aimed to evaluate the influence of sex and handedness on smartphone-based FTT performance. We developed an Android application for the FTT and recruited 40 males and 40 females to carry out three spatial designs on it (protocols I, II, and III). Participants’ performance was measured using the global, temporal, and spatial parameters of the FTT. We observed that for the performance in protocol I, handedness had a significant influence on global and temporal variables, while the interaction between handedness and sex had a greater influence on spatial variables. For protocols II and III, we observed that handedness had a significant influence on global, temporal, and spatial variables compared to the other factors. We concluded that the smartphone-based test is partly influenced by handedness and sex, and these factors should be considered during the evaluation of the smartphone-based FTT.
Acesso aberto (Open Access)
Efeito da competência leitora nas estratégias de organização perceptual da cena visual em escolares
(Universidade Federal do Pará, 2023-02) RESQUE, Deusa Priscila da Silva; MATOS, Felipe de Oliveira; http://lattes.cnpq.br/4207066833785568; https://orcid.org/0000-0002-4926-4694; PEREIRA JUNIOR, Antonio; http://lattes.cnpq.br/1402289786010170; https://orcid.org/0000-0002-0808-1058
The current Brazilian educational scenario, evaluated by different national and international indicators, has shown alarming results in mathematics, science and especially in reading. The country is in the last positions in all evaluations. For the change of this scenario, urgent educational measures that respect the student's biological and social development are necessary. The applied neurosciences to education emerge as a theoretical model of aid for pedagogical practices that aim to improve quality in education. An important contribution of neurosciences in education is focused on reading, through a theoretical/practical contribution on brain functioning those points more effective paths for literacy with a view to reading competence. In this sense, it was possible to understand that the human species has not yet developed a specific neural system for reading, using other brain structures for this function, ie literacy depends on a neural recycling process of brain structures associated with Sensory, motor and language functions, as is the case with brain regions associated with faces recognition, to accommodate the decoding of the written word. The aim of this study is to investigate reading in school -age children. To this end, the present thesis divided into two studies: Study 1 that investigates the inhibition of the generalization of letters in mirror in school -age children and the study 2 that investigates the relationship between reading competence and perceptual organization strategies of the visual scene in schools . Both studies were conducted in three public schools in the Belém do Pará Metropolitan Region, Brazil. Altogether two hundred and thirty -one subjects aged 6 to 10 years (113 boys, 8.2 ± 1.4 years and 118 girls, 8.2 ± 1.4 years), enrolled 1 to 5th years, were recruited, 1,2 ± 1.4 years old) elementary School. Among these eighty -eight subjects were students from school 1, fifty -two from school 2 and ninety from the school 3. In all, six tests were applied, each school participated in a different group of tests. Our results show that the performance of boys in the 6-10 year old is different from that of girls in the same age group for the reading competence test, with boys with higher performance, although it is not possible to establish differences between genders to the perceptual closure test. What's more, while boys performed significantly better in the rotation of letters in the older group, girls' performance was similar in both groups. This pattern is reverse for the mirror's task, with the older girls surpassing their younger counterparts and the boys performing similarly in both groups. Since the age period of our sample is not associated with large variations in reproductive steroid levels, we propose that the similarity of performance between younger and older girls in the mental rotation of letters may be associated with society's traditional attitudes and expectations and expectations about the relationship between spatial visual skills and gender. As for the mirror's task, while only girls showed a significant difference between the two age groups, the boys showed improvement, as expected by the mirror generalization inhibition to letters during reading. These findings are relevant to the development of more effective future strategies for optimizing the literacy process of school -age children, combining education and neuroscience. For this, more studies must be performed and the number of subjects investigated should be expanded.
Acesso aberto (Open Access)
O efeito do ruído espacial de cor sobre a discriminação limiar de luminância: investigação básica e aplicada em populações expostas ao mercúrio
(Universidade Federal do Pará, 2018-05-22) FARIAS, Letícia Miquilini de Arruda; CÔRTES, Maria Izabel Tentes; http://lattes.cnpq.br/3913689546568227; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718
Natural images are a complex set of color and luminance contrast that when combined in visual scene helps to create the discrimination of objects from the surrounding visual environment. A series of neural streams transmits the color and luminance information from the retina to the higher cortical centers. Several proposals have been made to study how the visual system processes the stimuli that combining color and luminance contrasts. This thesis has as main proposal to introduce a new stimulus to be used luminance discrimination task under chromatic noise masking. Thus, five experiments were carried out with focus this new paradigm to explore basic and applied questions about its use. Study 1 investigated the effect of color noise saturation on the threshold discrimination of luminance contrast. Study 2 investigated how the mosaic arrangement contributed to the contrast values of luminance contrast thresholds under the chromatic noise masking. Study 3 investigated the influence of the color content of the noise on the threshold discrimination of the luminance contrast. Study 4 investigated the influence of the polarity of the luminance contrast under the chromatic noise masking on the estimated threshold contrasts. Study 5 compared the values of threshold luminance contrasts under chromatic noise masking of two riverine populations of different Amazonian regions of the Pará State and exposed to different levels of mercury by feeding. The main finding of this thesis was that the luminance contrast thresholds varied as a function of the vector length of the chromatic noise values. The higher chromatic noise length, the higher luminance contrast threshold. The contrast threshold estimated by the non-mosaic stimulus exhibited significantly lower values than those estimated with mosaic stimuli (p <0.01). No statistical difference was observed between the contrasts threshold estimated around the five reference chromaticities at different saturation conditions (p> 0.05). The luminance contrasts thresholds estimated in the luminance decrement protocol were xiii significantly lower at all saturation levels than those estimated using the luminance increase protocol (p <0.05). There is no statistical difference between the thresholds of estimated luminance discrimination among riverine communities that were differently exposed to mercury (p> 0.05). The luminance contrasts threshold estimated by the new stimulus, described in this thesis, were influenced by chromatic and spatial noise, and by the polarity of the stimulus of luminance contrast. However, the different chromatic noise compositions did not exhibit any influence on the luminance discrimination. The presence of one or more color-sensitive visual pathways and luminance may be the physiological substrate of the mechanism underlying the luminance contrast perception of this new stimulus.
Acesso aberto (Open Access)
Efeitos anti-inflamatórios e neuroprotetores do extrato de gergelim (Sesamum indicum L.) em um modelo experimental de lesão aguda da medula espinhal de ratos
(Universidade Federal do Pará, 2016-06-10) PENHA, Nelson Elias Abrahão da; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
The spinal cord is a component of central nervous system (CNS) with crucial functions for locomotion, motor skills, somatosensory and authonomic control. Spinal injuries are among the more serious and debilitating pathological conditions to human health with large worldwide. The use of experimental models of spinal cord injury (SCI) is pivotal to understandthe SCI pathophysiology as well as search for treatments to minimize the neurological deficits and improve functional recovery. In this work, we aimed to investigate the neuroprotective and anti-inflammatory effects of supercritical gergelim (Sesamum indicum L.) extract in the acute phase of SCI in adult rats. Male Adult rats were submitted to spinal cord (SC) hemissection at T8. The sham (non lesioned) and control animals were treated with 5% tween(veicle), while treated animals received intraperitoneal (i.p) injections of Gergelim extract (150 mg/kg divided in two doses per day). Animals were allowed to recovery and were perfused at 1, 3 and 7 days post-lesion. 20 μm sections were obtained using a cryostat and stained with methylen blue, hematoxylin-eosin (HE), trichromic of Gomori and cresyl violet for gross histopathology. In addition, sections were immunolabeled with specific antibodies against neutrophils (anti-MBS-1) and activated microglia/macrophages (anti-ED1). The muscle force was assessed through electromiographic records performed in both control and treated animals at 1 and 7 days postlesion. The control animals presented progressive SC cavitation concomitant with neutrophil recruitment and microglia/macrophage activation. The treatment with gergelim extract induced tissue preservation and considerable decrease of neutrophil recruitment at 1 and 3 days, which was confirmed by quantitative analysis (ANOVA-Tukey, p<0.05). The gergelim treatment also decreased the microglia/macrophage activation at 7 days (ANOVA-Tukey, p<0.05). The electromiographic records revealed that the gergelim treatment improved the muscular force in about 50% compared to control animals. The results suggest that black gergelim seed extract is anti-inflammatory, neuroprotective and induces muscle force recovery in adults rats submitted to acute SCI. Future studies should confirm that a phytotherapic obtained from black sesame extract can be used as possible neuroprotective agent for human SCI.
Acesso aberto (Open Access)
Efeitos do transplante autólogo de células monocelulares da medula óssea após lesão incompleta da medula espinhal de ratos adultos
(Universidade Federal do Pará, 2017-03-30) SOUZA, Celice Cordeiro de; HAMOY, Moisés; http://lattes.cnpq.br/4523340329253911; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Spinal cord injury (SCI) causes permanent loss of neurological function below the level of injury, generating social and psychological physical consequences in patients. The pathophysiology of SCI involves complex processes, such as hemorrhage, excitotoxicity and inflammation, mainly generated by microglial cells. Despite advanced knowledge of pathological mechanisms, effective and approved therapeutic strategies for the treatment of lesions and their consequences are still lacking without serious adverse effects. Cell therapy may represent a good therapeutic strategy because it demonstrates good results in the modulation of the inflammatory environment of the lesion and by probable mechanisms of differentiation. In the present study, we investigated the action of bone marrow mononuclear cells (BMMC) in incomplete lesions (hemisection to the right of the spinal cord, T8-T9 segment) after 42 days of injury (chronic lesion). The cells were from the injured animal itself (autologous transplantation) and the transplantation was intramedullary, i.e. the cells were inserted near the site of the lesion. In the present study, the functional effects of transplantation were investigated through the BBB scale (Basso, Beatie and Bresnahan), which allows the motor function of the hind legs of the animals to be graded. The anti-inflammatory effects of BMMC were also investigated. Histological and immunohistochemical techniques using Cresila Violet staining and anti-ED-1 (microglial marker / activated macrophages) and anti-GFAP (fibrillar astrocyte marker) antibodies were used. Qualitative and quantitative analyzes were performed. For quantitative analysis, the number of field activated astrocytes and macrophages / microglia were counted using binocular microscope with counting gradient (0.0625mm2) in a 40x objective. The counting averages and the standard deviations obtained were plotted in Cartesian coordinates. The counting was as follows: on the right side of the spinal cord (lesion side) and three fields per medullary region (ventral funiculus - FV, dorsal funiculus - FD, lateral funiculus - FL, dorsal horn - CD, ventral horn - CV and intermediate gray matter-SCI), totaling 18 counting fields per section. Treatment with BMMC was not effective in improving the motor function of the injured animals when we compared the treated and untreated animals (means and standard deviations of the groups: false operated, n = 4, 21 ± 0, control, n = 4, 13,57 ± 3.88, treated, n = 5, 15.07 ± 3.46). In the qualitative analysis by means of the staining of Cresila Violet, treated animals presented better tissue preservation when compared to the untreated animals. In the quantitative analysis of microglial activation, we observed that treatment with BMMC reduced the activation of these inflammatory cells (control: 19.52 ± 7.79, treated: 10.04 ± 2.37), but did not significantly reduce the activation of the astrocytes (Mean of the groups: control 17.74 ± 2.757, treated 14.46 ± 5.283). The results suggest that further studies are needed to come up with an effective strategy for patients with SCI. A possible combined treatment with other strategies may turn out to be promising for patients' functionality.
Acesso aberto (Open Access)
Em direção à costa brasileira fugindo do inverno: rotas migratórias contrastantes e plasticidade diferencial dos astrócitos hipocampais
(Universidade Federal do Pará, 2018-01-04) OLIVEIRA, Marcus Augusto de; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
One of the largest seasonal events on the planet is the migration of birds from the Arctic to the southern hemisphere fleeing from winter and returning to the Arctic during the spring to the breeding season. Billions of individuals need to remember the routes learned during this epic journey and find the same places to rest and feeding. These birds can navigate thousands of miles with great accuracy, utilizing their spatial and temporal memories associated with the hippocampus, a key area for accomplishing this task. Recently, we have shown that the semipalmated sandpiper Calidris pusilla, after crossing the Atlantic towards the coast of South America, revealed significant changes in its hippocampal astrocytes. In fact, the hippocampal astrocytes of birds captured on the coast of Bragança in Brazil, compared with those of the hippocampus of individuals caught in the Bay of Fundy, Canada, were less numerous and exhibited shrunken branches. In the present work, we used another semipalmated shorebird, Charadrius semipalmatus, which, although having the same start and end points of C. pusilla migration, uses a different migratory strategy, performing a flight over the continent with stops for rest and feeding. Taking advantage of the opportunity offered by contrasting migratory flights, we tested the hypothesis that wintering bird species of the C. semipalmatus caught on the coast of Bragança (Brazil) would show greater morphological complexities than the hippocampal astrocytes of these migratory birds captured in the Bay of Fundy (Canada). Since the stands for food and rest, as well as the constant change in the landscape would constitute an enriched environment of multisensory stimuli, we expected to find in the individuals of C. semipalmatus captured in Bragança, an increase of the complexity, in opposition to the reduction in complexity previously found in C. pusilla. To test this hypothesis, we compared the three-dimensional (3-D) morphological characteristics of the adult C. semipalmatus astrocytes captured in the Bay of Fundy (n = 265 cells) with those of wintering birds captured in the coastal region of Bragança, Brazil, (n = 242 cells), and compared with the results obtained with C. pusilla. The Neurolucida program was used for three-dimensional reconstructions and the hierarchical cluster analysis (Ward’s method) was used to classify cells. This analysis showed two families of astrocytes, which we designated Type I and Type II, based on several morphological characteristics. Contrary to our expectations, Type I and Type II phenotypes showed, on average, independently of the species, lower morphological complexity after migration, and this reduction was significantly higher in Type I than in Type II. The magnitudes of these changes were significantly higher in C. pusilla than in C. semipalmatus. Taken together, these findings suggest that contrasting long-distance migratory flight strategies may differentially affect the astrocyte morphology and that distinct astrocyte morphologies may be associated with different functional roles during migration.
Acesso aberto (Open Access)
Enriquecimento ambiental reduz as alterações astrocitárias e a progressão da doença prion em modelo murino: ensaios morfométricos, estereológicos e comportamentais
(Universidade Federal do Pará, 2014-11-26) TORRES NETO, João Bento; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
It is well established that a sedentary lifestyle is a risk factor for a number of chronic diseases, including Alzheimer's disease. The neuropathology of Alzheimer's disease is characterized by amyloid deposits, neuronal loss, reactive gliosis, and vacuolization of the neuropil. Prion disease has been widely used as an experimental model for studying cellular and molecular aspects of chronic neurodegeneration much similar to that described in Alzheimer's disease. The impoverished environment of standard laboratory cages have been used to mimic a sedentary life whereas enriched environment has been used to mimic an active lifestyle. To test the hypothesis that an enriched environment can help to slow down the time course of chronic neurodegeneration associated with prion disease we induced prion disease in twenty Swiss albino female mice which had been housed at six months of age in an enriched environment (EE) or in a standard (SE) environment for five months. After this period bilateral stereotactic intracerebral injection of normal (NBH, n = 10) or infected brain homogenate (ME7, n = 10) were done. Infected brain homogenate was obtained from mice with clinical signs of terminal prion disease. The injected animals returned to their cages and housing conditions and grouped as follow: SE = NBH 5, EE = NBH 5, ME7 SE = 5, ME7 EE = 5. After three weeks post-injections the burrowing test was initiated. Burrowing is a sensitive task to hippocampal damage. 18 weeks after inoculation memory tests of object recognition was carried out. After behavioral tests animals were euthanized and their brains were histologically processed targeting astrocytic immunostaining of areas of interest. The progressive reduction of the activity of burrowing began in the thirteenth week after injection in group ME7 SE but only in the fifteenth week in ME7 EE group. The ability to recognize the displaced object in spatial memory test was impaired in ME7 SE group but remained normal in the other experimental groups. The test of discrimination between the new object and the family revealed no abnormalities. Quantitative analysis of GFAP immunostained cells were performed in the dorsal stratum radiatum of CA3 and in the polymorphic layer of the dorsal dentate gyrus. The stereological estimates of the total number of astrocytes and the volume of the cell body revealed that the number of astrocytes did not change but a significant hypertrophy occurs in CA3 cell bodies of ME7 SE and ME7 EE groups as compared to their respective controls. The average volume of the cell bodies of the ME7 EE group was smaller than that of the group ME7 SE. However similar analysis applied to the polymorphic layer revealed a significant increase in the number of astrocytes in the ME7 SE group in relation to NBH SE group and in ME7 EE compared to NBH EE. The volume of the cell body was also significantly higher in ME7 groups compared to their respective control groups. The three-dimensional morphometric analysis revealed significant increase in volume and surface area of the segments of astrocytic trees in diseased groups compared to controls. Environmental enrichment reduced swelling observed in the branches of ME7 group and increased the number of intersections of the distal branches in NBH EE group relative to NBH SE and the proximal branches in the group ME7 EE compared with ME7 SE. The use of cluster analysis and discriminant allowed the identification of morphometric parameters that contributed most to the distinction between the groups. To test the hypothesis that there are subfamilies of morphologically distinct astrocytes within each experimental group, we applied cluster and discriminant analysis to each experimental group and these analysis resulted in the formation of two distinct families in NBH SE group, three families in NBH EE and ME7 EE groups and four families in the ME7 SE group. The molecular and cellular changes, which lead to the formation of new families of astrocytes, and to the neuroprotection associated with an enriched environment slowing down the progression of the prion disease, remain to be investigated.
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.
Acesso aberto (Open Access)
Influências do tamanho da ninhada e da atividade física sobre a plasticidade glial na formação hipocampal em modelo murino
(Universidade Federal do Pará, 2014-02-07) VIANA, Lane Coelho; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Previous studies have shown significant effects of perinatal stress on cognitive performance in adulthood and during aging. However remains to be studied in detail as exercise at different stages of life helps to reduce these deficits. This is particularly true if we consider previous descriptions of extracellular matrix and glial cell changes, largely ignored in these studies. Thus, the aim of the present report is to investigate possible influences of litter size and physical activity on object recognition memory at adulthood and whether or not these influences affect glial plasticity and extracellular matrix of the hippocampal formation. To that end, we changed the litter size of Wistar rats to accentuate the degree of competition among siblings by functional teats and decrease the amount of maternal care per individual. During the suckling period, we have quantified the maternal care in litters of different sizes. At various time windows we submitted selected subjects to physical exercise on a treadmill, for 5 weeks, adopting the same training protocol. After exercise, some groups of adults and senile animals were submitted to the hippocampal-dependent object recognition memory test, sacrificed, and processed for selective microglia immunolabeling. Other groups of adult animals not subjected to behavioral tests were also euthanized and had one hemisphere used to record diffusional parameters in the hippocampal parenchyma while the other was used for selective immunolabeling to detect astrocytes, NG2 cells and reelin.We found that an increase in litter size was related to the reduction of maternal care, cognitive decline, altered morphology and proliferation of microglia, astrocytes and NG2 cells, as well as to a change in diffusion patterns in the hippocampal stroma. We also demonstrated that these changes may be reversed, at least partially, by physical activity and the extent of these beneficial effects are more pronounced in younger subjects. Finally, we demonstrated that ageing exacerbates microglial morphological changes induced by increased litter size and reduces memory performance.The molecular mechanisms associated to these effects remain to be investigated.
Acesso aberto (Open Access)
Investigação de danos visuais em pacientes diagnosticados com meningite criptocócica não associada à imunossupressão
(Universidade Federal do Pará, 2014-03-20) LACERDA, Eliza Maria da Costa Brito; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; SILVEIRA, Luiz Carlos de Lima; http://lattes.cnpq.br/9383834641490219
Cryptococcal meningitis is a severe infectious disease caused by Cryptococcus spp., which has high lethality and causes sensorial sequels. The most important sequels are visual impairments. The aim of this study was to describe the visual losses suffered by patients without immunosupression history, diagnosed with cryptococcal meningitis in order to indicate a possible mechanism and risk factors for the visual sequels. The work was composed by a case series study with cryptococcal meningitis without immunosupression history (n =7 patients, 14 = eyes) and an epidemiological study of all the cases of cryptococcal meningitis without immunosupression history notified during 14 years in the reference hospital of Para State (n = 113 cases). In the case series study, the visual functions of a sample of patients were studied by ophthalmological, psychophysical, and electrophysiological evaluation. The epidemiological study analyzed the medical records data focusing on visual impairment. It was observed that the studied patients in the case series study had visual acuity impairment. Even in patients without clinical complaints, color discrimination, luminance contrast sensitivity, and visual field were impaired. The results indicated central retina commitment as the principal responsible for a cascade of alterations that prevented the normal upstream image processing, at the visual cortex level. It is suggested that the observed visual dysfunction was due not only to optic nerve damage. The principal risk factors for the visual alterations observed in the epidemiological study were disease time before the beginning of the treatment and patient immunological response.
Acesso aberto (Open Access)
Investigação dos efeitos da cafeína e SCH58261 sobre as alterações comportamentais e no estresse oxidativo, e papel dos receptores A2A na potenciação de longo prazo após intoxicação por etanol em padrão binge em ratos fêmeas da adolescência a fase adulta
(Universidade Federal do Pará, 2022-11) PINHEIRO, Bruno Gonçalves; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Introduction: Binge consumption of ethanol is an intermittent and episodic pattern of ingestion involved in several brain disorders that affect adolescents, considered more susceptible to damage that persists into adulthood. In the deleterious effects of ethanol, an important intoxication mechanism is the overproduction of adenosine, which causes hyperexcitability in its receptors, generating behavioral changes and oxidative stress. These receptors are antagonized by caffeine, a bioactive compound that can modulate the deleterious overactivation of ethanol. Objective: The aim of this study was to investigate the effects of caffeine administration on behavioral changes related to locomotion, anxiety, cognition and oxidative balance induced by ethanol in the binge drinking pattern during adolescence. In addition, it aims to assess the contribution of A2A receptors in the observed changes, including long-term potentiation (LTP). Material and Methods: Female Wistar rats (35 days old; n = 102) were allocated into six groups: control (distilled water, v.o), ethanol (3 g/kg/day; 3 days on-4 days off, v.o) , caffeine (10 mg/kg/day, v.o), caffeine + ethanol, A2A antagonist SCH58261 (0.1 mg/kg/day, intraperitoneal - i,p) and ethanol + SCH58261. The animals were submitted to open field behavioral tests, object recognition and elevated plus maze. The oxidative biochemistry parameters of trolox equivalent antioxidant capacity (TEAC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) in the pre- frontal and hippocampus. LTP recordings in the medial prefrontal cortex (mPFC), ventral (vHip) and dorsal (dHIP) portions of the hippocampus of the control, ethanol, ethanol + SCH58261 and SCH58261 groups were evaluated through electrophysiology. Results: Caffeine prevented ethanol-induced behavioral impairments, including by blocking A2A receptors. In addition, it attenuated the oxidative stress induced by binge drinking by alternative A2A receptor pathways. Blockade of A2A receptors increased LTP levels in mPFC and vHIP, however decreased in dHIP. Conclusion: Caffeine showed neuroprotection in behavioral changes and oxidative stress induced by the binge drinking model in adolescent rats. In addition, blockade of A2A receptors mitigated the observed behavioral changes, with improvement of LTP levels in the prefrontal cortex and hippocampus, which suggests the contribution of this pathway to neuroprotection in deficits induced by ethanol exposure during adolescence.
Acesso aberto (Open Access)
Mascaramento por ruído de luminância sobre a discriminação de cor e luminância
(Universidade Federal do Pará, 2019-03-13) LOUREIRO, Terezinha Medeiros Gonçalves de; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718
Several psychophysical experiments were developed using pseudoisochromatics stimuli to evaluate color vision. It was observed that the color perception depends on the characteristics of the luminance noise present in the stimulus. In this thesis were developed two sets of experiments that study how the effects of spatial noise of luminance influence in the visual perception. In the first experiment we investigated the effect of the change in luminance noise amplitude in color discrimination. Eighteen trichromates and ten congenital discromatopics had their color vision evaluated by stimuli adapted from the Cambridge Colour Test and were genetically tested to diagnose mutations associated with congenital color vision deficiency. The stimuli were composed of mosaics of circles in a circular field of 5 ° of visual angle. A subset of the circles differed from the remaining field by chromaticity. The color discrimination was estimated in 4 stimulus conditions that differed in the amplitude of the luminance noise: (i) between 6-20 cd/m²; (ii) between 8 and 18 cd/m²; (iii) between 10 and 16 cd/m²; and (iv) between 12 and 14 cd/m². Six equidistant luminance values were used between the luminance noise limits and the mean luminance of the stimulus maintained in all four conditions. The color discrimination thresholds were estimated through a staircase procedure in 8 different chromatic axes. An ellipse function was fitted to the chromaticity data. The indicators of color discrimination were the area of the ellipse and the values of the eight thresholds of color discrimination. The rate of change of these indicators as a function of the luminance noise amplitude values was calculated as the value of the derivative of the linear function that best fit the function. In the second experiment, a subset of the circles differed from the remaining field by the luminance noise difference, forming the perception of a letter C. In this experiment we tried to evaluate the luminance discrimination in different luminance noise conditions (levels of 2, 4, 6, 10 and 14). Thirty healthy subjects were tested. A ladder procedure was used to control the average luminance of the luminance noise of the target. The luminance discrimination ranges between the mean luminance of the target and the background were the visual functional indicators. The results of the first experiment showed that the rate of variation of the ellipse area as a function of the luminance amplitude in dichromates was higher than in trichromates (p <0.05). It was observed that the low amplitude of the luminance noise (condition of 2 cd/m²) improves the color discrimination of the trichrome and dichromate subjects. Regarding chromatic axes, it was observed that there was a significant difference between the rates of variation of the threshold vector size as a function of the amplitude of the luminance noise of trichromates and dichromates in the axes 0º, 45º, 90º and 135º. The results of the second experiment showed that at lower luminance levels, noise significantly impaired the luminance discrimination (p <0.05) compared to the conditions of higher levels of luminance noise. It was also observed that the higher the luminance contrast present within the noise the worse the luminance discrimination. It is concluded that the modification of luminance noise can lead to significant modifications of the luminance discrimination for color discrimination.
Acesso aberto (Open Access)
Perda neuronal, ativação glial, neurogênese e alterações sensório-motoras após isquemia focal no córtex somestésico de ratos adultos
(Universidade Federal do Pará, 2012-09-26) CORRÊA, Vania Castro; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke is considered one of the most important causes of death and functional deficits in the world. Few neurological conditions are so complex and devastating, resulting in severe neurological deficits and death in the survivors. The cortical regions are commonly affected by stroke, resulting in sensory and motor loss. The establishment of neuropathological patterns in cortical regions, including the somatosensory area, is critical for the investigation of possible therapeutic interventions. In the present study, we investigated the patterns of neuronal loss, microgliosis, astrocytosis, neurogenesis and functional deficits in the primary somatosensory cortex of adult rats submitted to focal ischemia induced by microinjections of 40 pmol of endothelin-1 (ET-1). A total of 30 young adult Wistar rats (Rattus norvegicus) of Wistar, weighing between 250-280g were used in the study. The animals were divided into ischemic (N = 21) and control (N = 9) groups. They were perfused at survival times of 1, 3 and 7 days. The 7 days animals were submitted to behavioral tests to evaluate sensorimotor impairment. Sections were stained with cresyl violet, cytochrome oxidase and immunostained to identify neurons (anti-NeuN), activated and non-activated microglia (Iba-1), activated macrophages/microglia (ED-1), astrocytes (GFAP) and neuroblasts (DCX ). Statistical comparisons between groups were made by one analysis of variance (ANOVA) with Tukey post-hoc test. The animals showed ischemic sensorimotor deficits revealed by Bederson Neurological Scale, Paw Placement and corner tests. Microinjections of ET-1 induced focal ischemic lesion in the primary somatosensory cortex with neuronal loss and progressive astrocytosis and microgliosis mainly in the late survival times. The cytochrome oxidase histochemistry revealed the barrel fields, but unexpectedly marked a population of inflammatory cells with macrophage characteristics in the ischemic region. Increased numbers of SVZ neuroblasts were observed mainly in late survival times of ipsilateral hemisphere in comparison to contralateral side and control animals. There was no significant migration of neuroblasts to the ischemic cortex. The results show that microinjections of ET-1 are an effective method for inducing tissue loss and sensorymotor deficits in the primary somatosensory cortex of adult rats. It was evident that the SVZ is influenced by distant ischemic events distant and that macrophage populations seem to increase the cytochrome oxidase expression. The implemented experimental model can be used in future studies, in which potential neuroprotective drugs can be tested to minimize the described neuropathological alterations.
Acesso aberto (Open Access)
Plasticidade aumentada no córtex pré-frontal de ratos com a remoção de redes perineuronais
(Universidade Federal do Pará, 2016-11-01) RODRIGUES, Klebson de Jesus Araujo; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170
Aging is associated with decreasing brain plasticity, especially after the closure of the critical periods of plasticity (a sensitive limited period in life of elevated brain plasticity). Some brain regions may be particularly affected by aging, such as prefrontal cortex (PFC), which has a key role in the organization of higherorder cognitive aspects, the executive functions, including attention, set-shifting, working memory, decision making, etc. Decline of plasticity in the PFC and the brain is attributed mainly to the appearance of a structure called perineuronal net (PNNs) which enwraps the cell body and dendrites of many classes of neurons. PNNs are extracellular matrix structures consisting of chondroitin sulfate proteoglycans, hyaluronan, link proteins and tenascin, and are involved in the control of experience-dependent cortical plasticity and the closure of critical periods. Degradation of PNNs with the enzyme Chondroitinase ABC (ChABC) restores juvenile forms of plasticity in the adult brain. Here, we examined the developmental time course of PNN formation in the medial PFC (mPFC) of male rats ranging in age from the seventh postnatal day (PND) to 11 months. We used the lectin Vicia villosa agglutinin that binds to glycosaminoglycan chains present in the PNNs. We also investigated whether the digestion of PNNs by bilateral injection of ChABC in the mPFC may open a new window of increased plasticity in adult rats, evaluated by two executive function tests: object recognition and spontaneous alternation. We found that immature PNNs were observed in PND 20 animals, but mature PNNs were seen only after PND 75-90 and a mature form appeared around 5 months of age. In addition, our results showed that enzymatic PNN removal promoted a significant increase in performance in the ChABC-treated animals in both behavioral tests. The present study reveals for the first time the temporal development of PNN formation in the rat mPFC. We also show that the degradation of PNNs with ChABC not only promotes plasticity but also potentiates cognitive abilities in adult animals.
Acesso aberto (Open Access)
Plasticidade de modalidade cruzada em córtices sensoriais adulto
(Universidade Federal do Pará, 2018-12-21) DIAS, Ivanira Amaral; BOTELHO, Eliã Pinheiro; http://lattes.cnpq.br/6276864906384922; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644
The central nervous system (CNS) neural circuitry is highly dynamic and is continuously modified by sensory experience, in a process we call neuroplasticity, which gives the CNS the ability to adapt to changes in the sensory periphery and / or in response to environmental stimuli . This ability of the CNS remains lifelong, although it is more intense during early stages of development, especially during the critical plasticity period. The main goal of the present work was to evaluate the effects of bilateral sensory deprivation on cross modal neuroplasticity in the visual, somatosensory, and auditory primary cortices od adult rats. Animals (Rattus novergicus) (authorization CEUA/UFPA: 141-13) were divided into three experimental groups: a control group (CTL), an unimodal deprivation group (DEP), in which the animals were subjected to visual deprivation by bilateral enucleation, and a bimodal deprivation group (DDEP), whose animals were submitted to both visual and whisker deprivation bilaterallly. After 60 days of sensory deprivation, the rats were perfused and the brains were sectioned in the coronal plane for immunohistochemistry procedures aimed at revealing the activation of immediate early genes (c-Fos). The results showed that after bilateral visual deprivation the number of c-Fos+ neurons decreased in the visual cortex (** p < 0.0056), increased in the auditory cortex (** p <0.0099), and had no effect in the somatosensory cortex. Bilateral visual and whisker deprivation decreased the number of c-Fos+ neurons in the visual cortex (* p <0.0268) but did not have any effect in the somatosensory and auditory cortices.