Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2375
O Mestrado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).
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Item Acesso aberto (Open Access) Análise in vitro do potencial antitumoral do conjugado LDE/Paclitaxel comparado à formulação do comercial Taxol sobre linhagem celular C6 de glioblastoma de rato(Universidade Federal do Pará, 2022-09) ANJOS, Ana Carolina Brito dos Anjos; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; https://orcid.org/0000-0003-2909-949X; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072Glioblastoma, also known as grade IV astrocytoma, is one of the most common and aggressive types of tumors in the central nervous system. Among the characteristics of this type of tumor, the following stand out: infiltration of isolated tumor cells in normal brain tissue, cell proliferation, angiogenesis and intense necrosis. Currently, the main therapeutic approach consists of surgical resection followed by radiotherapy and chemotherapy. However, in most cases, the tumor is not well defined, spreading through the brain region, which makes it difficult to fully resection. In addition, the removal of tissue from this region can leave several sequels. Consequently, patients have high rates of recurrence and low rates of survival. Another problem in the treatment of this type of tumor is due to the lining of the blood-brain barrier that restricts the entry of molecules and substances, including drugs. Thus, this project aims to analyze the antineoplastic effects of the association of a nanoparticle called LDE with a structure similar to low-density lipoprotein (LDL) that will act as a carrier of the drug paclitaxel (PTX), commercially known as Taxol®, it is a chemotherapeutic drug whose cell antiproliferative action has been proven in the treatment of other types of cancer, such as breast and refractory ovarian cancers. For this purpose, the mouse glioblastoma cell line C6 was used for performing in vitro analysis regarding the effects of these treatments on aspects of viability, cytotoxicity and cell death by apoptosis, using the ApoTox-GloTM Triplex Assay kit (Promega Corporation), which performs the three previously mentioned analyses, sequentially. To evaluate growth and drug effect on PTX and LDE/PTX treatment groups, approximately 1x106 cells were cultured in 96-well microplates at concentrations of 0.01; 0.1; 1 and 10 μM in the times of 24h, 48h and 72h. The control was not exposed to the compounds, containing only DMEM culture medium. Results obtained after treatments with PTX and LDE/PTX were expressed as mean ± standard deviation and analyzed by one-way (cytotoxicity) and two-way (viability and apoptosis) ANOVA, followed by Tukey's post hoc test. Differences were considered significant when p ˂ 0.05.Item Acesso aberto (Open Access) Avaliação das alterações no sistema somatossensorial como estratégia para o diagnóstico precoce e tratamento de pacientes com transtorno do espectro autista - TEA(Universidade Federal do Pará, 2020-01-31) SANTA MARIA, Bruna Castro; Amira Consuêlo de Melo Figueiras; http://lattes.cnpq.br/6213115471891287; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806Autism spectrum disorder (ASD) is characterized by persistent deficits in communication and social interaction in multiple contexts and restricted and repetitive patterns of behavior, interests or activities. The most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), presented the addition of "hyper and hypo-reactivity to sensory input or unusual interests in sensory aspects of the environment" as defining diagnostic characteristics of autism. Individuals with autism often report tactile sensitivities, such as stiffness or withdrawal when touched. Thus, the objective of this study was to identify changes in somesthetic sensitivity that may assist in strategies for early diagnosis and intervention of patients with autism. Clinical observations and questionnaires were carried out among the participants, where it was observed that children from control group showed minimal alterations in somesthetic reactivity when compared with the ASD group. It was found that 90% of the participants in the TEA group did not play with different consistencies; 70% do not play with gelatinous objects and materials of different textures, as well as showing an aversion to certain fabrics and / or clothing labels; 62% do not participate in games that get wet or smeared and walk or walked on tiptoe and 50% avoid hugging and / or physical contact, showing that in children with autism it is possible to notice early hypo or somesthetic hyperreactivity, which could support the diagnosis and early intervention strategies.Item Acesso aberto (Open Access) Avaliação de microRNAs circulantes na esquizofrenia: da desregulação epigenômica a potenciais biomarcadores(Universidade Federal do Pará, 2021-03) RODRIGUES, André Luiz de Souza; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099; https://orcid.org/0000-0002-4872-234XIntroduction: Schizophrenia is a serious and complex pathology that affects about 0.5-1% of the world's population. For the clinical diagnosis of schizophrenia, there are clinical criteria to be evaluated, which include both positive and negative symptoms. In the origin of the disease, there is a close relationship between environmental stimuli, and strong evidence shows that these stimuli have the ability to act on epigenetic mechanisms, which act in the regulation of gene expression. MicroRNAs (miRNAs) are stable and potentially reliable biomarkers, and some miRNAs have been previously identified as potential biomarkers for schizophrenia in peripheral samples. Objective: To evaluate the expression profile of circulating miRNA's in patients with schizophrenia (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) in relation to control individuals negative for the disease. Methods: Analytical, case-control, cross- sectional study using samples previously collected from patients diagnosed with Schizophrenia (N = 650) and control group (N = 924), who adequately met the inclusion criteria. The samples were analyzed after RNA extraction through its quantification and techniques for obtaining reverse transcriptase reaction and real-time quantitative polymerase chain reaction. All data were analyzed using IBM SPSS22 statistical program. Results: Using the peripheral blood collection method with the intention of finding possible biomarkers for schizophrenia, an increased expression of the miRNA’s miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652 was observed in several scenarios analyzed, confronting the case and control groups, as well as variables within the case-group, demonstrating potential diagnostic value.Item Acesso aberto (Open Access) Avaliação dos níveis extracelulares de GABA e glutamato no sistema nervoso central de camundongos infectados com Plasmodium berghuei ANKA(Universidade Federal do Pará, 2024-11) LIMA, Renato Mateus Santos de; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369Cerebral malaria (CM) caused by Plasmodium falciparum results in high mortality, especially in children under 5, with up to 25% of survivors experiencing neurological sequelae such as cognitive impairment and seizures. The neurochemical mechanisms behind these impairments are not well understood. This study aimed to characterize changes in the levels of the neurotransmitters glutamate (GLU) and γ-Aminobutyric acid (GABA) in the central nervous system (CNS) during experimental cerebral malaria (ECM). ECM was induced in Swiss mice with Plasmodium berghei ANKA (PbA), and the animals were monitored for parasitemia, survival, and neurological impairments using the Rapid Murine Coma and Behavior Scale (RMCBS). On the 7th day post-infection (d.p.i), blood-brain barrier (BBB) disruption was assessed using Evans Blue dye, and glial cell evaluation was performed by immunofluorescence. Results showed that PbA-infected mice began to succumb to CM by the 6th d.p.i, with 100% mortality by the 10th d.p.i. Behavioral impairments were observed from the early stages of infection. Significant BBB permeability changes and increased expression of glial activation markers were noted in infected mice. There was a marked increase in GLU levels in the brain and cerebellum on days 3, 5, and 7 post-infection. GABA levels increased on days 3 and 5, returning to control levels by day 7. These findings indicate significant neurochemical alterations in GABAergic and glutamatergic neurotransmission, accompanied by neurological and vascular impairments, suggesting their involvement in the development of neurological symptoms in CM.Item Acesso aberto (Open Access) Avaliação neuropsicológica de deficits cognitivos em pessoas vivendo com HIV (PVHIV)(Universidade Federal do Pará, 2024-08) GONÇALVES, Samilly Palheta; RODRIGUES, Anderson Raiol; ROCHA, Fernando Allan de Farias; http://lattes.cnpq.br/3882851981484245; https://orcid.org/0000-0002-6148-1050The introduction of antiretroviral therapy resulted in a reduction in opportunistic infections associated with HIV, consequently reducing the incidence of most neurological diseases in HIV-positive patients. However, neurocognitive changes associated with HIV (HAND) remain at a significant prevalence, even in individuals using antiretroviral drugs. The present study aimed to evaluate possible cognitive deficits in HIV-positive patients and characterize the clinical profile of neurocognitive manifestations in the Northern region of Brazil. 30 HIVpositive patients were evaluated, treated at the Health Care Center for Acquired Infectious Diseases (CASA DIA), in Belém do Pará. It was possible to verify a decline in neurological functions, which affect the functional capacity of these PLHIV, with emphasis on the cognitive domain of memory and attention, where it was possible to identify through IADLs, IHDS and CANTAB.Item Acesso aberto (Open Access) Efeitos da terapia motora baseada em movimentos de dança nas funções da teoria da mente e do ritmo Mu de pessoas com doença de Parkinson(Universidade Federal do Pará, 2023-08) VILHALVA, Jade Thalia Rodrigues; KREJCOVA, Lane Viana; http://lattes.cnpq.br/2604693973864638; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644; https://orcid.org/0000-0003-3794-4710Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects brain regions whose neural circuitry is responsible for controlling voluntary movements. In addition to motor symptoms, PD patients have non-motor symptoms that drastically affect their quality of life. These include cognitive alterations, among which deficits in working memory, deficits in executive functions and in the ability to deduce the mental states of others (Theory of Mind: ToM) stand out, and may also be related to the functions of mirror neurons (MN). The MN are neurons activated when a person performs or observes a given action, thus performing “internal” simulation of the observed acts, a necessary process for the ability to recognize emotions and intentions in the ToM. Their activity is influenced by prior training of observed motor actions and can be recorded using electroencephalography (EEG) through changes in the Mu band wave amplitudes (alpha 1 waves) detected when an individual observes the actions of another person. The present work investigated the effects of motor therapy on electroencephalographic activity and its correlations with MT functions in patients affected by PD. For this purpose, electroencephalographic evaluations were performed to investigate desynchronization patterns characteristic of mirror neuron activity, in addition to the Reading the Mind in the Eyes (RME) and Faux Pas Recognition (FPR) tests. We evaluated patients diagnosed with PD (n=09), under pharmacological regimen, Hoehn and Yahr 2-4, of both sexes and with mean age of 62.9 ± 7.1 years and mean of 5.8 ± 1.3 years of diagnosis , in time windows before joining the project after twelve months of participation in 2 weekly sessions of motor therapy in dance. Tabulated data were analyzed using Student's t-test. No significant differences were observed in the evaluation parameters of the FPR test in the Test and Retest temporal windows, whereas in the RMT test the average score obtained by the participants in the Test was 9.7 points, while in the Retest the average was 11.3 points with observed significance (p=0.0148), whereas electroencephalographic statistical analysis (TRPs) showed significant results in the level of desynchronization of alpha 1 waves (p=0.014 and p=0.010) during specific electrophysiological evaluation. The data showed that although the individuals did not show improvement in performance in most components of the analyzed TM tests, the electrophysiological results indicate alteration of specific cortical activity related to the activation of the mirror neuron system, influenced by motor therapy in dance, which may configure then, as an adjuvant therapeutic option in the management of motor and non-motor symptoms of PD.Item Acesso aberto (Open Access) Efeitos neuroprotetores e anti-inflamatórios do óleo de copaíba (Copaifera reticulata Ducke) em ratos adultos submetidos a isquemia do córtex motor por microinfecções de Edotelina-1(Universidade Federal do Pará, 2019-02-15) SILVA, Paulo Rodrigo Oliveira da; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072Stroke is a neural disorder caused by interruption of blood flow in vessels that irrigate the brain (ischemic stroke) or rupture of these (hemorrhagic stroke), causing cognitive, sensory and / or motor deficits. With the exception of thrombolytic use, which has a very narrow therapeutic window and is little used, there are no other pharmacological treatments or cellular therapy available for this pathological condition. Thus, it is necessary to search for new treatments, such as the development of neuroprotective agents. The Amazon is a rich source of natural products, but its therapeutic actions for diseases of the central nervous system (CNS) have been little investigated. In this work, we have investigated the neuroprotective and anti-inflammatory actions of copaiba oil-resin (COR). Adult Wistar rats were submitted to focal ischemia by microinjections (80pMol/μl) of endothelin-1 (ET-1) directly into the motor cortex and were treated with daily doses of COR (400mg / kg) or 5% tween. The animals were perfused at 7 days after the injury. The histopathological analysis was performed by Nissl staining (brain) and hematoxylin-eosin (liver and kidneys). Immunohistochemistry was performed for labeling of neurons (anti-NeuN), astrocytes (anti-S100) and caspase (anti-caspase-3). Morphometry showed a reduction in the lesion size area (copaiba-treated animals (15.96 ± 1.53 mm2); control animals (28.82 ± 2.65 mm2). Histopathological examination of the liver and kidneys did not find changes indicative of toxicity. In the quantitative analysis, neuronal preservation was observed, but no statistical difference was noticed between the groups regarding astrocytes analysis (S100+ cells). The COR-treated group showed an increase in caspase-3 expression. It is concluded that COR may play a neuroprotective role, contributing to neuronal survival in the area of ischemic penumbra, but future work is needed to find out the mechanisms underlying this phenomenon.Item Acesso aberto (Open Access) Melatonina previne danos cerebrais e déficits cognitivos induzidos pela infecção por Plasmodium berghei anka em modelo murino de malária cerebral(Universidade Federal do Pará, 2021-05) ATAIDE, Brenda Jaqueline de Azevedo; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369Cerebral malaria is characterized by permanent cognitive impairments in Plasmodium-infected children. Antimalarial therapies show little effectiveness to avoid neurological deficits and nervous tissue alterations elicited by severe malaria. Melatonin is a well-recognized endogenous hormone involved in the control of brain functions and maintenance of blood–brain barrier integrity. The current study has evaluated the effect of melatonin on the histological alterations, blood–brain barrier leakage, and neurocognitive impairments in mice developing cerebral malaria. Swiss mice infected with Plasmodium berghei ANKA strain was used as cerebral malaria model. Melatonin treatment (5 and 10 mg/kg) was performed for four consecutive days after the infection, and data have shown an increased survival rate in infected mice treated with melatonin. It was also observed that melatonin treatment blocked brain edema and prevented the breakdown of blood–brain barrier induced by the Plasmodium infection. Furthermore, hematoxylin and eosin staining revealed that melatonin mitigates the histological alterations in Plasmodium-infected animals. Melatonin was also able to prevent motor and cognitive impairments in infected mice. Taken together, these results show for the first time that melatonin treatment prevents histological brain damages and neurocognitive alterations induced by cerebral malariaItem Acesso aberto (Open Access) Modelo de hemiparkinsonismo por 6-hidroxidopamina em primatas Sapajus apella: características comportamentais e histológicas(Universidade Federal do Pará, 2024-10) PEDROSA, Laís Resque Russo; KREJCOVÁ, Lane Viana; http://lattes.cnpq.br/2604693973864638; GOMES, Bruno Duarte; http://lattes.cnpq.br/4932238030330851Despite considerable side effects and decreasing effectiveness over time, the treatment for Parkinson's disease (PD) has remained largely unchanged for over 50 years. However, several aspects of the disease's pathophysiology remain poorly understood. The development of new therapies and the elucidation of mechanisms related to the disease are among the biggest current challenges in neuroscience research. In this context, non-human primate (NHP) experimental models are particularly relevant due to their high phylogenetic proximity, encephalization rate, and complex motor and behavioral repertoire, confer high predictive power for clinical outcomes. The 6-hydroxydopamine inoculation model of parkinsonism mimics relevant features of PD and may represent an important experimental refinement in primates. The present study aimed to develop a model of hemiparkinsonism induction in Sapajus apella primates, characterizing the behavioral and histological aspects. For this purpose, adult male Sapajus apella monkeys were subjected to motor tests to observe motor performance before and after unilateral injection of 6-OHDA in the nigrostriatal pathways at concentrations of 4 (N=1), 10 (N=1) and 40 (N=1) mg/μl in the dominant hemisphere. As a surgical control (N=1), one animal underwent surgery containing only solvent. Stereotaxic coordinates for the 12 6-OHDA inoculation sites were calculated based on individual Magnetic Resonance Imaging (MRI) images. Immunohistochemistry for tyrosine hydroxylase (TH) was performed on 50 μm coronal sections of the midbrain. As a statistical analysis, two-way ANOVA was used to verify possible differences in behavioral parameters and neuronal exclusion between groups, considering the dominant (therefore affected) and non-dominant hemispheres. There were significant changes in motor patterns of dominance and manual preference after surgical intervention. 6-OHDA induction in the nigrostriatal pathways appears to be a good method of inducing parkinsonism with the induction of detectable symptoms in primates.