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 perfil do número de cópias e transcriptoma de pacientes com gliomas e em linhagens de glioblastomas tratadas com pisosterol
(Universidade Federal do Pará, 2018-10-17) FERREIRA, Wallax Augusto Silva; OLIVEIRA, Edivaldo Herculano Corrêa de; http://lattes.cnpq.br/0094007714707651
Central Nervous System Tumors (CNS) account for approximately 2% of all cancers. Although the incidence of CNS tumors is small, compared to other neoplasms, these tumors are among the most serious human malignancies because they affect the organ responsible for the coordination and integration of all organic activities. Gliomas represent approximately 80% of all intracranial tumors, typically affecting adults, with a high incidence between 40 and 65 years of age. Although numerous anti-glioma drugs have already been developed, they induce adverse reactions and their therapeutic effects are not satisfactory. The objective of this study was to evaluate and compare the profile of Copy Number Variation (CNV) and gene expression of patients diagnosed with gliomas and in glioblastomas cell lines (U87-MG, U343, AHOL1 and 1321N1) treated with pisoterol. For rhe experiments done with the cell lines treated with pisoterol, we demonstrated that they were highly sensitive to pisoterol treatment. This drug reduced the number of live cells in a dose-dependent manner. In addition, we demonstrated that after 48h of exposure to pisoterol, all cell lines were blocked in G2/M. Finally, we demonstrate that the pisosterol can modulate the expression of several genes of ATM/ATR pathway, promoting apoptosis. We demonstrated on genomic scale that all the cell lines had more genes that were significantly down-regulated than up-regulated after the treatment with pisosterol. For the experiments done with the gliomas biopsies, we demonstrated that only 11 genes (TNFRSF1A, SNAPC2, CASP8, IRAK3, GPX3, FZD9, TFAP2C, CDH1, RPRM, POU4F3 and MGMT) exhibited changes in the pattern of methylation in all grades analyzed. In addition, the methylation pattern of these 11 genes had correlations with some clinicopathological characteristics, such as age, sex and histological grade. And finally, we made a molecular characterization describing the CNVs of the gliomas originating from Belém-PA.
Acesso aberto (Open Access)
Efeitos anti-inflamatórios e neuroprotetores do extrato de gergelim preto (Sesamum indicum L.) em um modelo experimental de isquemia estrial
(Universidade Federal do Pará, 2024-03) SANTOS, Ijair Rogério Costa dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Acidente Vascular Encefálico (AVE) é uma neuropatologia caracterizada como o surgimento súbito global ou focal de déficits da função neurológica de duração superior a 24 horas ou que leve a morte, cuja única causa reside na origem vascular. Estudos sobre a incidência, comprometimento físico e mortalidade enquadram o AVE como a segunda causa de morte no mundo e a principal complicação orgânica que leva às disfunções físico-neurológicas, frequentemente, graves e permanentes. A indução do AVE em animais de experimentação e o entendimento de sua fisiopatologia, bem como a busca de tratamentos que minimizem os danos neurológicos e estimulem a recuperação morfofuncional do indivíduo afetado são temas de grande relevância científica e clínica. Neste estudo, investigamos os possíveis efeitos neuroprotetores e/ou anti-inflamatórios do extrato supercrítico de gergelim preto (Sesamun indicum L.) após lesão isquêmica focal por microinjeções de 80 pmol de endotelina-1 no estriado de ratos adultos, usando as coordenadasestereotáxicas: 1,2 mm, anterior-posterior; 2,5 mm, médio-lateral; 4,0 mm, dorsoventral. Após a indução do AVE, os grupos controles foram tratados com tween a 5% e os tratados receberam 150 mg/kg de gergelim, ambos, por via intraperitoneal, em duas doses diárias de 75 mg/kg. A neuropatologia foi obtida em secções encefálicas com 50 e 20 μm de espessuras e coradas com violeta de cresila, para identificar a área de lesão, e/ou imunomarcadas por anticorpos específicos à identificação de neurônios (anti-NeuN), astrócitos (anti-GFAP) e micróglia (anti-ED1). Secções de 5 μm de espessura de rim e fígado corados por métodos histológicos e histoquímicos não mostraram alterações morfológicas nas células que compõem esses órgãos essenciais, sugerindo baixa toxicidade do extrato. Todas as secções coradas e/ou imunomarcadas foram visualizadas em microscópio óptico e seuscampos mais ilustrativos, em todos os tempos de sobrevida e grupos experimentais,foram capturados digitalmente e editados em computador. A quantificação das célulasNeuN+(neurônios), micróglia/macrófagos (ED1+) e astrócitos (GFAP+) na área de lesão, três secções por lâmina, todo campo ao redor de lesão por secção, com auxílio de uma gradícula de área 0,0625 mm2 na ocular possibilitou o teste t-Student à análise estatística entre os grupos e o uso do programa Microsoft Excel à plotagem dos gráficos. Por fim, uma caracterização da citotoxicidade in vitro, bem como a verificação do índice de acidez do extrato revelou baixa acidez e mínima agressividade em células sanguíneas, que ratifica o uso do extrato supercrítico em estudos que visem otratamento de doenças agudas e crônicas no SNC.
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)
Análise transcriptômica das linhagens celulares B103 e C6 expostas à ação do metilmercúrio
(Universidade Federal do Pará, 2023-04) BONFIM, Laís Teixeira; FERREIRA, Wallax Augusto Silva Ferreira; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/009400771470765; https://orcid.org/0000-0001-6315-3352
The intensification of anthropogenic activities produces a high rate of environmental pollution, mainly in water bodies, where the contamination by metals has become an object of great interest, due to their inability to support such load. Mercury (Hg) is a naturally occurring metal that can be used in the manufacture of home products such as fluorescent lamps, fungicides, and germicides. The entry of Hg into the food chain occurs through the methylation of Hg2+ ions into MeHg. After methylation, Hg is considered highly toxic to humans, and among the main target organs of this intoxication we can mention the brain, since MeHg easily crosses the blood-brain barrier and can accumulate in different brain areas. It is known that, once in the CNS, MeHg can cause extensive cellular damage, such as DNA damage, oxidative stress, neuroinflammation and cell death in both neurons and glial cells. Thus, the objective of this study was to analyze the transcriptomic alterations of cell lines B103 and C6, derived from neuroblastoma and glioma of Rattus norvegicus, exposed to the action of methylmercury. For this, the expression microarray technique was used to evaluate the global profile of gene expression after 24h of MeHg exposure. Our results demonstrate that MeHg induces significant alterations in gene expression of the two cell lines evaluated. The alterations were more prominent in the C6 cell line, in which a greater amount of differentially expressed genes was observed. Among the genes differentially expressed of the B103 cells we can highlight the genes Cdc42se2 (log2 FC -4.055713), Dcx (log2 FC 3.618981) and 4930449C09Rik (log2 FC 3.5129156) at a concentration of 0.1 μM. As for the exposure of 2.8 μM, the genes with the highest FC were Crem (log2 FC -4.027875), Otoa (log2 FC 3.501512) and Dcx (log2 FC 3.423433). In addition to the abovementioned genes, the genes Trim14, Gm14169, Gm30871, Otoa and Dcx were shared between the two exposed groups. As for the C6 lineage, ten transcripts with FC above 3 (Aldh1l2, Dac1, Rps4l, Zbtb46, 6430573p05Rik, Tcf12, Awat2, Muc3, Dclre1b, Slc38a6) are highlighted. In the 6.3 μM treatment, only three genes were altered more than 3 times (Rps4l, Ankdr44 and 2610318N02Rik). It is also noteworthy that three genes were shared between treatments (Rps4l, Lamb 3 and Gm 41386).
Acesso aberto (Open Access)
A tomada de decisões no judô: o que se diz e o que se faz? Relação entre tomada de decisões e perfil neurocognitivo
(Universidade Federal do Pará, 2023-03) RIVERA, Luis Felipe Sarmiento; GOUVEIA JUNIOR, Amauri; http://lattes.cnpq.br/1417327467050274; https://orcid.org/0000-0003-1710-9662
There are two ways to think about how the decision process is done. The process can be automatic and having psychomotor characteristics, or mediated by linguistic process -in a deliberated way-. Moreover, martial arts bring an environment with high emotionality, where the anxiety is present. The objective of this study is to understand how the decision-making process, the anxiety and the impulsivity is presented in a combat physical activity, a Judo fight, that demands constant decisions and responses with limited time. To do this, there were to groups of participants (30 judo fighters and 15 non-fighters). One of the groups watch a video and anticipated the fighter’s movement with a questionary, and the other group was recorded in a judo fight. Both groups also performed an impulsivity test and an anxiety test. Each participant had more than 4,5 years of training and was an active competitor. There were found differences in the decisions made by the participants in the fight and the decisions that the participants told they would perform, specifically, when they were going to execute and action. Moreover, there was a significant difference in the anxiety levels of the group of fighters compared to controls, where the fighters had higher anxiety levels than controls. There were none significative differences in impulsivity between the groups. The results of the study shown how is cognition in Judo fighters, indicating where to focus the training and competition programs of the fighters.
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)
Dinâmica de sucção disfuncional em lactentes com anquiloglossia
(Universidade Federal do Pará, 2023-11) CUNHA, Bruna Mendes Lourenço; SILVA FILHO, Manoel da; http://lattes.cnpq.br/2032152778116209
Introduction: Breastfeeding is widely recommended as an exclusive diet until 6 months of age and continued until two years or more. Its benefits are numerous and proven, including improving the immune system, a nutrient-rich diet and craniofacial development from the sucking movement. However, not all babies are able to breastfeed due to some difficulties, with ankyloglossia. Known as tongue tie, it can restrict tongue movements, making breastfeeding difficult and, in some cases, being responsible for early weaning. Objective: Compare infant suction in babies with and without ankyloglossia using a microprocessor-controlled pressure sensor coupled to a pacifier. Method: Fifty-five infants from 0 to 2 months of age underwent clinical examination for ankyloglossia, after which they were offered a silicone pacifier connected to the pressure acquisition device and suction activity was recorded. Thus, we extracted the frequency of sucks within a burst, the average suck duration, the burst duration, the number of sucks per burst, the maximum amplitude of sucks per burst and the inter-burst interval. Results: The key difference in newborns with ankyloglossia in relation to control was that they perform longer bursts of suction activity. Conclusion: The longer burst durations are likely a compensatory strategy and may underlie the pain reported by mothers during breastfeeding. We therefore propose a method for objectively quantifying some parameters of infant suction capacity and demonstrate its use in assisting the evaluation of ankyloglossia.
Acesso aberto (Open Access)
A infecção por Plasmodium berghei (ANKA) induz um quadro de encefalopatia hepática em modelo murino de malária não complicada
(Universidade Federal do Pará, 2024-02) KAUFFMANN, Nayara; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247; https://orcid.org/0000-0003-4022-8096; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369
Introduction. The main changes in hepatocellular dysfunction associated with malaria are liver failure, hepatosplenomegaly and increased liver enzymes. Several studies have already elucidated that such liver changes can be caused by increased ammonia levels, which can consequently lead to dysfunction in the central nervous system (CNS), causing hepatic encephalopathy, culminating in an increase in the inflammatory response, cerebral edema, deregulation of neurotransmitters and cognitive and locomotor changes. Objective: To characterize possible changes in the central nervous system resulting from liver injury induced by Plasmodium berghei ANKA infection in a murine model of uncomplicated malaria. Methodology. For this, mice of the Balb-c lineage (20- 25g) were used between 45-54 postnatal days (CEUA nº 2229290317), inoculated with ~106 parasitized erythrocytes intraperitoneally. The experimental design was divided into two parts: Firstly, the survival curve, parasitemia, body mass, clinical signs, hepatic and histological changes, neurochemistry, presence of cerebral edema, vascular extravasation, inflammatory response, behavioral changes and quantification of blood levels were characterized. ammonia in the control and PbA groups. Subsequently, a treatment with lactulose was carried out to verify whether the changes found in the previous experiments were due to the increase in ammonia levels in the animals' brains. For this purpose, the groups were divided into: control group, lactulose 3mg/kg, PbA and PbA+lactulose 3mg/kg, in which the survival curve, parasitemia and locomotor activity were evaluated using the SHIRPA protocol. The results were expressed as mean+standard deviation. ANOVA (one way) was performed, post Tukey test, considering p<0.05 as significant. Results. Our data demonstrated that the PbA group presented changes in liver functions such as increased levels of AST and ALP, BT and BD, morphological changes such as hepatosplenomegaly, in addition to histological changes showing inflammatory infiltrate, deposition of malarial pigment and Kupffer cell hyperplasia, thus demonstrating a picture of liver failure. After characterizing the liver injury, we sought to understand whether these changes could generate impairment in the CNS, which we observed cognitive and motor impairment, in addition to changes in the levels of the neurotransmitters GABA and glutamate, accompanied by an increase in the inflammatory response, cerebral edema and dysfunction in the liver. blood-brain barrier. Once liver failure was demonstrated and, consequently, the presence of cognitive and behavioral changes, we sought to evaluate ammonia levels in the brains of control and PbA animals in the initial phase of infection. In this sense, the quantification of ammonia levels showed an increase on the 10th d.p.i., in brain tissue when compared to the control group, in which the levels were within expectations in relation to locomotor activity, when applying the protocol in the infected and treated group with lactulose, it was possible to observe that the PbA group showed changes in motor behavior, when compared to the control group. In contrast, the PbA+Lactulose 3mg/kg group showed an attenuation of cognitive and behavioral changes, showing that therapy with lactulose can attenuate the cognitive condition regarding motor behavior, muscle strength and tone, reflexes, and sensory function. Conclusion. We conclude that liver failure causes hepatic encephalopathy in a murine model of uncomplicated malaria, which culminates in changes in the central nervous system, by increasing ammonia levels in the brain, and by sequestering ammonia with the help of treatment. with lactulose at a dose of 3mg/kg, it can attenuate the neurological damage of animals with uncomplicated malaria, demonstrating that the behavioral changes come from a condition of hepatic encephalopathy, caused by increased levels of ammonia in the cortex of infected animals.
Acesso aberto (Open Access)
O papel da biologia molecular no diagnóstico, epidemiologia molecular e perfil de sensibilidade de cepas de M. leprae em região endêmica da Amazônia Brasileira
(Universidade Federal do Pará, 2023-10) BOUTH, Raquel Carvalho; SILVA, Moises Batista da; http://lattes.cnpq.br/5525661855611118; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125
Leprosy is a chronic disease, disabling and difficult to diagnose in all its clinical manifestations. The aims of this study were to identify the laboratory marker that presents greater sensitivity and specificity for diagnosis, to genetically understand the strains of M. leprae circulating in the Pará State and to evaluate the region drug resistance reality. A multidisciplinary team evaluated 833 individuals using different strategies at URE Dr. Marcello Candia, and in 14 municipalities in Pará. All individuals were clinically evaluated, and biological samples were collected for comparative analysis of the results of slit skin smear microscopy, molecular detection of the bacillus by qPCR RLEP in ear lobes, IgM Anti-PGL-I antibodies titration, and histopathological lesion skin biopsy, lesion qPCR RLEP, and M. leprae whole genome sequence. 351 cases were clinically diagnosed, divided into groups: individuals with classic and non-classic clinical manifestations, asymptomatic cases and 482 healthy contacts. The comparative analysis of the results demonstrated that ear lobe RLEP detection presented greater sensitivity, specificity and agreement with the clinical diagnosis (72.5, 70.4 and Kappa = 0.42 respectively), followed by skin biopsy (sensitivity= 65.8%), Anti-PGL-I serology with 61.2% (52.2 specificity), slit smears skin (41.7%) and histopathology (25.0%). The RLEP association to serology, showed an increased in laboratorial correlation with the clinic diagnosis (Kappa= 0.55). The circulant streains evaluation, we detected that the most frequent profile was profile 4N (52/66- 78.8%), followed by 4P subtype (4/66- 6.1%), 3I (9/66 -13, 6%), and 1D (1/66- 1.5%). In the drug resistance analysis, we obtained 3/101 (3%) mutation in folP1 gene, conferring dapsone resistance. 1/40 (2.5%) gyrB mutations, conferring quinolones resistance. The gyrB resistant strain also had mutation in folP1, and in the fadD9, ribD, pks4 and nth genes, considered a hypermutant strain. Our findings showed that qPCR RLEP molecular test associated with Anti-PGL-I serology were a good tool for leprosy laboratorial diagnosis, and that type 4 strains, originating in Africa, are the most frequent type in the Amazon. And we find drug-resistant strains, and a hypermuted strain circling in the region. The strains were resistant to the current polychemotherapy regimen and the alternative drug regimen.
Acesso aberto (Open Access)
Viabilidade e eficácia da telerreabilitação e da cartilha de exercícios para pessoas com doença de Parkinson residentes em uma região da Amazônia brasileira: um ensaio clínico randomizado
(Universidade Federal do Pará, 2023-12) RAMOS, Luciana Fernandes Pastana; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306; LOBATO, Bruno Lopes Santos
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder, and the current treatment involves pharmacological intervention and physiotherapy. Telerehabilitation, which involves remote support and guidance for patients undergoing rehabilitation, can potentially improve access to physiotherapy services for people with Parkinson's disease, especially those who face geographic barriers to healthcare. The primary aim of this study was to assess the feasibility and efficacy of a telerehabilitation program for people with Parkinson's disease living in an underrepresented community of the Brazilian Amazon. We conducted a parallel-group, single-center, single-blind, randomized clinical trial involving 19 participants diagnosed with Parkinson's disease from Belém, Brazil. Participants were assigned to a 4-week individual telerehabilitation program or a booklet-based exercise program (control group). Assessments were conducted before the intervention, immediately after the intervention, and 4 weeks after the end of the intervention. We showed that our telerehabilitation program had high adherence among patients, with minimal adverse effects. Both telerehabilitation and booklet orientation reduced the time to complete the Timed Up and Go test. In conclusion, our telerehabilitation or booklet-based exercise program was feasible and effective for people with Parkinson's disease in an Amazonian setting. This trial was registered at the Registro Brasileiro de Ensaios Clínicos (ReBEC) under the identifier: RBR-6sz837s.
Acesso aberto (Open Access)
Avaliação do óleo essencial de pau-rosa (Aniba rosaeodora Ducke) em modelo de depressão induzida por álcool em ratas adolescentes
(Universidade Federal do Pará, 2023-08) SANTOS, Éverton Renan Quaresma dos; MAIA, José Guilherme Soares; http://lattes.cnpq.br/1034534634988402; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Depression is a prevalent disorder worldwide, which affects the functionality and quality of life of the people. The linalool-rich rosewood essential oil (Aniba rosaeodora Ducke) displays activities on the central nervous system (CNS), including of antidepressant-type. The work aimed to evaluate the effect of the essential oil in adolescent female rats through a model of binge drinking-induced depression. The essential oil was extracted by hydrodistillation and analyzed by a dual system of gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (CG-FID). The in vitro antioxidant capacity of the essential oil was determined in the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging assay. Female Wistar rats, 29 days old, received distilled water or ethanol (3 g/kg/day) orally in 4 binge episodes, and saline solution or rosewood oil (35 mg/kg) intranasally once a day for 28 days. After the experimental treatment, splash and forced swimming tests were performed. The brain-derived neurotrophic factor (BDNF) and S100B gene expression, biological parameters of the oxidative stress and levels of pro-inflammatory cytokines were determined in the prefrontal cortex and hippocampus. The OEPR+EtOH group increased self-cleaning time and decreased immobility time, both significantly compared to the EtOH group in the splash and forced swimming tests, respectively. The essential oil behavioral effects were related to positive modulation of BDNF and S100B genes, to restoration of glutathione (GSH) and Trolox equivalent antioxidant capacity (TEAC) levels, in addition to the attenuation of the increase of thiobarbituric acid reactive species (TBARS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) induced by alcohol. The results suggest that essential oil improved the alcohol-induced depressive profile through a neuroprotective mechanism by positively modulating the gene expression of neurotrophic factors, rebalancing the antioxidant status and attenuating the inflammatory process, possibly due to the linalool action.
Acesso aberto (Open Access)
Método baseado me cromatografia líquida de alta eficiência para analisar a atividade dos transportadores de GABA no sistema nervoso central
(Universidade Federal do Pará, 2022-08) MORAES, Edinaldo Rogério da Silva; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
The GATs are the membrane proteins responsible for the uptake of GABA in the central nervous system. Alterations in GAT activity are implicated in several neurological diseases, including retinopathies. The present study describes an alternative method to determine GAT activity in tissue preparations of the central nervous system, using high performance liquid chromatography (HPLC) with fluorescence detection. The GABA concentration in the medium was determined using the o-phthaldehyde (OPA)-derivation protocol validated by the Brazilian Health Regulatory Agency (ANVISA) and the United States Food and Drug Administration (US-FDA). The GAT activity in the retinal preparations was determined through the evaluation of the GABA uptake, which was measured by assessing the difference between the initial and final concentrations of GABA in the incubation médium (Δ𝐺𝑎𝑏𝑎 = [𝐺𝑎𝑏𝑎] 𝑡_0 − [𝐺𝑎𝑏𝑎] 𝑡_𝑒𝑛𝑑). The evaluation of the GAT kinetics returned values of Km = 382.5 ± 32.2 μM and Vmax = 34 nmol/mg of protein. The data also demonstrated that the GABA uptake was predominantly Na+ and temperature-dependent, and was also inhibited by incubation with nipecotic acid, a substrate of GABA transporters. Taken together, these findings confirm that our approach provided a specific measure of GAT activity in retinal tissue. The data presented here thus validate, for the first time, an alternative, simple and sensitive method for the evaluation of GAT activity using high performance chromatography on preparations of the central nervous system.
Acesso aberto (Open Access)
Semelhanças cognitivas inesperadas entre idosos e jovens: variabilidade e desempenho cognitivo
(Universidade Federal do Pará, 2023-08) JARDIM, Naina Yuki Vieira; TORRES, Natáli Valim Oliver Bento; http://lattes.cnpq.br/1927198788019996; https://orcid.org/0000-0003-0978-211X; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Interindividual variability in cognitive performances has been investigated as they may provide important clues about the multivariate age-related cognitive decline. In the present work, we searched for cognitive variability, similarities, and differences between older and young people. For this, we used hierarchical cluster and canonical discriminant function analysis of cognitive scores using specific and sensitive tasks from the Cambridge Neuropsychology Test Automated Battery - CANTAB. Among 415 tested volunteers, three distinct cognitive groups were found, mainly based on working memory and episodic memory scores: group 1 (94% young adults) was composed almost exclusively of young adults, while groups 2 (82% older adults) and 3 (95% older adults) were composed predominantly of older adults. Although group 1was the youngest group with the highest level of education compared to the other groups, 18% of young people shared similar performances with older group 2 while 5% shared cognitive similarities with group 3. As compared to group 1, predominantly older groups 2 and 3 had equally lower scores in working memory, but as compared to group 3, group 2 showed greater performances in reaction time, sustained attention, and episodic memory. When the hierarchical cluster and discriminant function analyzes were limited to the same age group, we found 4 and 5 distinct clusters among young adults and older people respectively. Episodic memory, sustained attention, and reaction time most contributed to group formation in the older, while working memory and sustained attention contributed to cluster formation of young adults. Cognitive variability across subjects showed significant dispersion in rapid visual processing, spatial working memory, reaction time, and paired associated learning. The comparative analysis of these differences showed that they do not occur in the same direction and magnitude between individuals, cognitive domains, and tasks. We found that older adults with greater education and a more active lifestyle must have greater cognitive reserve and, therefore, deviated less from the reference group of young adults. Taken together, our data highlight the importance of studying variability as an instrument for the early detection of subtle cognitive declines and to interpret results that deviate from normality.
Acesso aberto (Open Access)
Significado da expressão de p16INK4A e da perda de heterozigosidade do gene PTEN no carcinoma epidermóide bucal relacionado ao papilomavírus humano
(Universidade Federal do Pará, 2023-06) KATO, Valdenira de Jesus Oliveira; ALCÂNTARA, Diego Di Felipe Ávila; http://lattes.cnpq.br/1794240697748468; https://orcid.org/0000-0001-5045-2265; BURBANO, Rommel Mario Rodríguez; http://lattes.cnpq.br/4362051219348099; https://orcid.org/0000-0002-4872-234X
The p16 and PTEN genes are part of the family of tumor suppressor genes commonly associated with the inactivation of a variety of human cancers. The loss of its expression has been studied worldwide in oral squamous cell carcinoma (OSCC). In this study, we evaluated the hypothesis that p16 cooperates with inactive PTEN during OSCC pathogenesis, especially in tumor aggressiveness and proliferation. For that, 119 OSCC samples were used in which the relationship between HPV infection, p16 expression and PTEN mutations were evaluated throug himmunohistochemistry (IHC), western blot, immunofluorescence and sequencing techniques. The results of this study demonstrated that PTEN has high positivity in patients with more advanced tumor size (p < 0.01) and lymph node metastasis (p = 0.02). Statistical analysis showed that p16 expression was strongly associated with the presence of HPV (p<0.0001), but that its aberrant expression is not related to altered PTEN (p=0.52). It was also observed that 60% of the samples in stage IV (advanced stage of the tumor) were statistically associated with the presence of mutation. It is concluded that PTEN and p16 are suppressor genes that control tumor progression. In the current study, PTEN showed great erreactivity in advanced stages of the disease (greater than seven times). p16 was strongly associated with HPV, but did not show a significant association with any clinical-pathological factor analyzed. Both proteins are of great importance in the prognosis of patients. Viral presence has been shown to decrease tumor aggressiveness. Lesions in advanced stages have a shorter survival, in addition, the presence of mutation was more commonly observed in advanced stages of the disease. It was observed that smoking patients witht he absenceof p16 are significantly associated with a survival rate twice as low.
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)
Expressão gênica durante o desenvolvimento ocular e regulação de assimetria de opsinas na espécie Anableps anableps, peixe de quatro olhos
(Universidade Federal do Pará, 2022-11) SOUSA, Daniele Salgado de; SCHNEIDER, Patrícia Neiva Coelho; http://lattes.cnpq.br/9584217233879031
The ocular development is a complex process orchestrated by several events that include: cell specification, morphogenesis and differentiation. All these developmental and functional processes are extremely conserved among living vertebrate species, however, unique adaptations are sometimes observed, such as in fish of the genus Anableps. Unlike most fishes, which use their eyes to explore a submerged world, in Anableps anableps (Anablepidae: Cyprinodontiformes), the eye is adapted for the simultaneous perception of a world above and below the water line. These exceptional adaptations include: duplicated corneas and pupils, as well as a specialized retina region associated with simultaneous aerial and aquatic vision, and which have asymmetrical gene expression. Recently, by transcriptomic analysis of the developing eyes of A. anableps, 20 non-visual opsin genes were identified to be asymmetrically expressed between pre- and post-duplication stages of corneas and pupils. Thus, here, we analyzed by in situ hybridization the gene expression of a bistable opsin (parapinopsin) and a neuropsin (Opn5) in A. anableps larvae. Our data showed that the pattern of gene expression of these opsins is symmetrical between the dorsal and ventral retina, respectively, with expression in the ONL, INL and GCL layers. We also investigated the expression of three non-visual melanopsin genes (opn4x1, opn4x2, opn4m3), one eleost multiple tissue opsin (tmt1b), and two visual opsins (lws and rh2-1) in the dorsal and ventral retinas of juvenile A. anableps, after changing the photic conditions in which the juvenile fish were. Then, we showed that in the transition from an environment of high turbidity to one of clear water, opsins have their expression patterns changed. Additionally, by immunofluorescence, we revealed the expression of Lamin A/C, proteins expressed as part of eye development in A. anableps as well as in other developing organisms, as well as in adult individuals. Therefore, we believe that the information described here elucidates many aspects of the molecular mechanisms behind the development and adaptive plasticity of A. anableps’ eyes.
Acesso aberto (Open Access)
Estudo do desenvolvimento auditivo da habilidade de fusão binaural
(Universidade Federal do Pará, 2022-04) ARAÚJO, Francisca Canindé Rosário da Silva; SILVA FILHO, Manoel da; http://lattes.cnpq.br/2032152778116209
Introduction: Binaural Interaction (BI) allows the introduction of auditory information (in the brain as a function of differences in perception of intensity or time of acoustic stimuli). Allows you to assess the action and integrated co- operative of the brainstem in lower understanding. As the maturation of the central nervous system occurs in the craniocaudal direction, the response to this ability may change during the course of development. Objectives: To normalize and compare the development with increasing age of response in the binaural diffusion test (BPT) with digital low-pass (LP) and high-pass (HP) filters in normative listeners. Methods: Prospective, cross-sectional and observational study. A total of 120 years were evaluated, in different age groups (6 to 8 years old, 10 to 12 years old, 14 to 16 years old and 20 to 30 years old) with TFB, filter at Fc 500/1700 Hz digital Finite Impulse Response type order 4096, with null phase and 5000 between 18 and 30 years with unfiltered speech material. Results: a progressive improvement in performance with increasing age (ANOVA (one-way): p<0.0001). There was a significant difference between the filtered words, age and the unfiltered p < (Dunnet: any filtered words,01). The difference between the age groups was significant (Tukey: p<0.01), less for the results obtained in the age groups of 6-8 and 10-12 years and of 14-16 and 18- 30 years. Discussion: IB is a skill that evolves with age development and NC fabrication. Final considerations: The interpretation of the TFB should take into account the performance by age group of the patients. This is important for future applications of these tests in people with Auditory Processing Disorder.
Acesso aberto (Open Access)
Tamanho de tumores da região selar como um preditor de perdas psicofísicas e eletrofisiológicas de campo visual
(Universidade Federal do Pará, 2019-11) LOBÃO, Carlos Augusto Ferreira; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; https://orcid.org/0000-0002-4525-3971
Sellar region tumor growth represents an important cause of visual loss due mechanical compression of the optic nerve apparatus. Many investigations have used non-invasive tools to evaluate the visual field consequences of this damage, and good association have been reported between psychophysical and electrophysiological perimetry. Few reports have considered the tumor size as predictor of the visual field loss. Objectives: In the present study, it was evaluated the association between tumor size and visual perimetry alterations measured by a psychophysical method, the Humphrey Visual Field Analyzer perimetry, and an electrophysiological method using the multifocal visual evoked cortical potential (mfVECP). Methods: The analyzed sample was composed by 14 patients diagnosed with sellar tumors on magnetic resonance imaging. The number of sectors with negative visual responses for both methods was counted. A simple logistic regression analysis was used to evaluate the association between the tumor dimensions and the visual field features. Results: Three patients had preserved visual fields, three patients showed hemianopic defects, and eight patients had generalized visual field losses at both evaluations. It was observed that the three maximum diameters of the tumor and total tumor volume had different predictive abilities regarding the extent of visual field loss when using psychophysical and mfVECP data. The maximum craniocaudal diameter of the tumor was the better predictor of the psychophysical measurements, while for mfVECP results, all tumor dimensions and volume had similar value to predict visual field losses. Conclusion: Sellar region tumor size is a predictor of visual loss found on psychophysical and electrophysiological visual perimetry. This correlation has potential to assist in the clinical intervention, and to prevent the irreversible visual impairment caused by these tumors to the patient.
Acesso aberto (Open Access)
Pez-cebra (Danio rerio) como modelo de bienestar animal
(Universidade Federal do Pará, 2022-10) VASQUEZ, Jhon Jairo Buenhombre; GOUVEIA JUNIOR, Amauri; http://lattes.cnpq.br/1417327467050274; https://orcid.org/0000-0003-1710-9662
Zebrafish has become an important model for various disciplines such as neuroscience and the testing of new pharmacological molecules. Therefore, the way in which it is housed and the consequences of its accommodation on its well-being represent an important aspect to study. Very few studies have evaluated the effect of environmental enrichment on the welfare of zebrafish and its negative or positive impacts have yet to be elucidated. An important challenge is to establish the consequences not only of the presence of enrichment but also of its loss. Likewise, the form of presentation of a stimulus, either predictably or unpredictably, influences the physiological and behavioural responses of the animal. Therefore, the form of presentation of the enrichment represents another important aspect to assess. The evaluation of emotional (affective) states is crucial for the study of zebrafish welfare, in particular to evaluate the influences of the environment on the animal. However, directly assessing these states is difficult due to their subjective nature. Therefore, the current approach focuses on estimating them from the resulting physiological and behavioral components. Today there are robust standardized tests that assess and correlate neuroendocrine responses with well-established behavioural assessment criteria for stress and anxiety in zebrafish. However, there are no similar tests to measure positive emotional states in this species. An alternative metric to assess both the positive and negative affective states of animals is the cognitive bias. These tests allow researchers to infer an individual's emotional state from cognition. Therefore, the evaluation of apparently negative (Unpredictable conditions and absence or loss of enrichment) and positive ones (Predictable conditions and presence or gain of enrichment) accommodation contrasts through a type of cognitive bias (cognitive judgment bias (CJB) in zebrafish may constitute a promising model to understand the effects of housing on affective states and well-being in this fish. Additionally, it has been shown that individual variations such as personality influence the central nervous system, behaviour and cognitive judgment bias results in other species. These differences and their impacts on zebrafish have not yet been studied. Consequently, the general objective of this thesis was to establish if the cognitive judgment bias can be used in zebrafish for the evaluation of positive and negative emotional states produced by environmental modifications and its relationship with personality.
Acesso aberto (Open Access)
Topografia de células ganglionares alfa na retina de roedores da Amazônia
(Universidade Federal do Pará, 2022-05) SAMPAIO, Gabriela Santos Alvarez; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; https://orcid.org/0000-0002-4525-3971
Introduction: The visual system of Amazonian rodents of the suborder Hystrichomorpha has been widely described, but little is known about the topography of alpha ganglion cells, which play a role in processing the vision of moving stimuli. Agouti (Dasyprocta aguti), paca (Cuniculus paca) and capybara (Hydrochoerus hydrochaeris) rodents are three different species of Hystrichomorpha that have a different circadian cycle and lifestyle. Objectives: To quantify alpha ganglion cell density and analyze cell body size according to eccentricity in the retina of agouti, paca and capybara. Methods: Three agouti, paca and capybara retinas from the pre-existing retinal collection at the Eduardo Oswaldo Cruz Laboratory of Neurophysiology at UFPA were used. Retinal collection were stained by the Nissl corpuscle staining method and direct counting was performed under a Zeiss optical microscope. The density of alpha-like ganglion cells was analyzed in different retinal eccentricities, such as in the visual range, area centralis, dorsal and ventral regions. Result: Analyzing the entire retina, the mean density of alpha-like ganglion cells in the agouti was 94.7±5.05 cells/μm2, in the paca it was 28.7±2.03 cells/μm2 and in the capybara it was 28.7±2.03 cells/μm2. of 101.03±24.42 cells/μm2. The presence of areas with high density of alpha ganglion cells was observed in the temporal region of the retina of the three rodents, and the agouti was the species that showed the most accentuated specialization of this type of ganglion cells. The cell body area of alpha ganglion cells that showed the highest frequency in the agouti retina was 200 μm², in the paca retina it was 300 to 600 μm² and in the capybara it was 300 to 500 μm². Conclusion: It is concluded that there is a relationship between ecology and density of alpha ganglion cells in the retina of large Brazilian rodents, so that those with diurnal habits have retinas with a greater number of these cells and with greater specialization in the temporal region.