Navegando por Assunto "Sistema nervoso central"

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Acesso aberto (Open Access)
Alterações de expressão gênica na linhagem de glioblastoma humano U87 após exposição ao MeHg e HgCl2
(Universidade Federal do Pará, 2016-12-02) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
The organic and inorganic forms of mercury have been pointed as important contaminants in several world regions due to its toxicological characteristics. Various studies have reported that the intoxication by methylmercury (MeHg) and mercury chloride (HgCl2) can lead to central nervous system impairment. It is generally agreed that glial cells are important for the mechanisms responsible for cellular protection against the damages caused by the mercury. However, little is known about the influence of the mercury in the cells genome. Hence, in the present study we did a complete mapping of the humam glial cells genetic network after mercury exposition with the aim to indentify the possible genetic alterations that occurred via the organic and inorganic forms of mercury. Our results demonstrated that U87 lineage cells are more sensitive to MeHg exposition when compared with HgCl2 exposition. Using an analysis of the concentration curves the LC50 was obtained from 28.8μM and 10,68μM after 4h and 24h exposition to MeHg and a LC50 of 92.25μM and 62.75μM after the same time periods exposition to HgCl2. Regarding the genic pool, our results have shown that both metal forms led to alterations in the genic dosage where the MeHg exposition was highly influenced by the concentration and time, whereas the HgCl2 exposition seemed have been strongly influenced by the exposition time. In total there were 205 indentified genes with a lower genic dosage and 188 genes with elevated expression, (Fold change > 5) after 4h exposition and 5μM of MeHg, and 204 down-regulated genes; and 180 up-regulated genes after HgCl2 exposition in the same concentration. The analysis after 24h exposition showed 90 down-regulated genes and 3 up-regulated genes after 1μM of MeHg; 116 genes were down-regulated and 66 genes were up-regulated after a 10μM exposition of MeHg. As for the HgCl2, there were 98 down-regulated genes and 73 up-regulated genes for the groups exposed to 5μM of HgCl2; 326 down-regulated genes and 66 up-regulated genes for the groups exposed to 62,75μM of HgCl2. Our dataset suggests that both mercurial forms are able to alter the cell genetic expression profile thus interfering in important signaling paths prone to gives rise to biochemical impairments and glial cells phenotypes.
Acesso aberto (Open Access)
Análise comportamental e eletrofisiológica do uso de glicocorticoides no sistema nervoso central em modelos animais de depressão
(Universidade Federal do Pará, 2017-01-31) CARDOSO, Keilla Gisele Mendonça; GOMES, Daniela Lopes; http://lattes.cnpq.br/0014255351015569; LIMA, Silene Maria Araújo de; CV: http://lattes.cnpq.br/8961057812067156
Dexamethasone is a glucocorticoid widely prescribed in Medicine, used as immunosuppressant and anti-inflammatory as well as fluoxetine, which is an antidepressant, serotonin reuptake, which can be used at some point while aiming their respective purposes. The aim of this study was to evaluate the electroencephalographic abnormalities in animals administered with these drugs as well as the behavioral effects evaluated in an animal model of depression, forced swimming. The study was conducted in adult male Wistar rats subjected to administration of dexamethasone acute dose of 4 mg/kg, 24 hours before electrocorticographic record, and chronic, administered for seven days every 24 hours at a dose of 4 mg/kg i.p. Fluoxetine was administered at a dose of 5 mg/kg, for seven days orally with a similar tool the orogastric tube, gavage procedure. After administration, the electroencephalographic parameters of drug activity were recorded and analyzed. When comparing the acute administration of dexamethasone with chronic, there were no statistical differences, but there was a trend towards decreased Theta and Gamma force for chronic use. The group, who received fluoxetine averaged amplitude of 2,661 ± 0,5850 mV²/Hz x 10-3, proving fluoxetine efficacy in controlling depression caused by forced swimming. For the group received dexamethasone chronically and fluoxetine to reverse the power of the middle frame was 0.4758 ± 0.2514 mV²/Hz x 10-3, as there is no statistical difference between the dexamethasone group and dexamethasone fluoxetine, fluoxetine failed to reverse depressive symptoms caused by dexamethasone. In the forced swimming, the fluoxetine group had decreased fluctuation time, mean time of 45.33 ± 23.26 seconds, demonstrating that the group was not depressed. In the group administered with dexamethasone chronic form and assessed the possibility of reversing depressive disorder with fluoxetine immobility time average was 169.8 ± 24.5 seconds indicating that fluoxetine had no effect on the depression caused by chronic application of dexamethasone. We conclude from this study that the glucocorticoid cause changes in electrocorticogram and depression in the forced swimming test (FST). Fluoxetine got no effect on the rats subjected to the FST, after the use of dexamethasone.
Acesso aberto (Open Access)
Análise de alterações no número de cópias envolvendo os cromossomos 1p e 22 em meningiomas de baixo grau
(Universidade Federal do Pará, 2013-12-13) SILVA, Geanny Pereira da; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/0094007714707651
Meningiomas are the second most common type of primary brain tumor, originating in the meninges covering the brain and spinal cord. They show slow growth, and are found more often in the CNS, being benign in most case, although there are also cases of meningiomas classified as malignant. At the cytogenetic level, meningiomas are the most well studied tumors in humans: studies in CNS tumors have shown that most cases had chromosomal abnormalities, and the most common alterations in theis type of tumor are the loss of one copy of chromosome 22 and deletion of the short arm of chromosome 1. These alterations have been associated with the tumorigenesis process, because they are found mostly in low-grade tumors, particularly deletions involving chromosome 22. Thus, the aim of this study was to analyze the occurrence of copy number alterations (CNAs) involving chromosomes 1p and 22 meningiomas grade I and II, and in addition to verifying the existence of other recurrent rearrangements through the application of high resolution comparative genomic hybridization (array - CGH ). Tumor samples were collected from eight patients. All samples showed gains and losses of various chromosomal segments. Except for one case, all others showed, in different degrees though, more deletions than amplifications. Loss of 1p segments was observed in all samples. Some CNAs were recurrent, being found up to six out of the eight cases. Pair 22 showed CNV in all samples, but the total monosomy was observed in only two of the eight samples. The global analysis of CNAs in all samples showed that, although changes 1p and 22 were the most frequent observed alterations, as expected, other genomic regions had also alterations in various samples, indicating a possible involvement of these modifications in the process of tumorigenesis and tumor progression. For instance, alterations in pairs 9, 12 and 17, have been observed in other studies and were correlated with atypical and anaplastic meningiomas. Our data indicate the existence of a larger number of genomic alterations in low-grade meningiomas, disagreeing partly with the assumption that these tumors are characterized by a small number of changes, usually involving pair 22 and, less frquently, loss of 1p. However, the fact that these tumors present alterations that are classically found in meningiomas, even benign, such as deletions in 1p and 22q, may be an indication that these changes must be linked with the early events of origin in meningiomas, as already suggested several times by other authors . In conclusion, these alterations remain important markers in meningiomas, and the relationships of these and other CNAs with the response to different treatments and recurrences should be the next step after cytogenomic characterization based on array-CGH has been completed.
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/2085871005197072
Glioblastoma, 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.
Acesso aberto (Open Access)
Análises moleculares da região controle do DNA mitocondrial de astrocitomas na população paraense
(Universidade Federal do Pará, 2012-06-06) COSTA JÚNIOR, Carlos Antonio da; ANSELMO, Nilson Praia; http://lattes.cnpq.br/6518287721873199
The central nervous system cancer represents 2% of all malignancies in the world population and 23% of cases of childhood cancer. In Brazil, an estimated 4,820 cases of cancer in men and women in 4450 to the year 2012. Gliomas are tumors of the central nervous system formed from glial cells, making up over 70% of brain tumors. The most important property of gliomas is the ability of immune evasion. Age, ethnicity, gender and occupation may be considered risk factors for the development of gliomas, and are twice as common in African-Americans. The astrocytoma is the most common glial tumor, constituting about 75% of cases of gliomas. These tumors are classified into four levels according to the World Health Organization. Mitochondrial DNA is related to the development and progression of various types of tumors. Mitochondrion is responsible for cellular energy balance and is involved in triggering apoptosis responding to oxidative stress. Mutations in DLOOP can change DNA replication rates and increase the developing cancer risk. We analyzed 29 samples astrocytoma classified according to the WHO. Our data suggest that low-grade astrocytomas may be related to genetic inheritance, making some patients with specific mutations or polymorphisms more susceptible to the risk of developing the disease, and high grade may be related to prolonged exposure to carcinogenics. Polymorphisms and mutations have been identified which correlate with some risk of developing astrocytomas and disease progression. The insertion of two or more nucleotides at microsatellite regions may cause instability and contribute to the cancer onset. Deletion at the site 16132 may be a high-grade astrocytoma marker, as well as insertion of two or more cytosines to the site 16190 can be an astrocytoma specific marker. Heteroplasmy may be decisive for the emergence and / or progression of high-grade astrocytomas.
Acesso aberto (Open Access)
Aumento da ativação neuronal e de marcação de BDNF após degradação das redes perineuronais em modelo experimental de privação sensorial
(Universidade Federal do Pará, 2016-09-23) AGUIAR, Gisele Priscila Soares de; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644
The central nervous system (CNS) has the ability to processing and store information collected from the environment, and modifies and adapt under environmental stimuli diversity. However, It has low regeneration capacity after injury or neurodegenerative disease. Several works are demonstrating cellular and molecular mechanisms implicated in CNS plasticity, such as chondroitin sulfate glycosaminoglycans (GAGs-SC) important components of the extracellular matrix from nervous tissue, responsible for synaptic stabilization, toconcentrateof growth factors and ions around neurons. Removing CSPG of the nervous tissue, we can (re)opens a potential plasticity window in the CNS. The goal of our work is to evaluate the influence of removal of GAGs-SC on neuronal activity, via cFos immunolabeling, and BDNF proteins levels at the barrel cortex, under an experimental model of sensory deprivation (vibrissectomy) during critical period of plasticity. To do that, we used 18 rats (Rattus novergicus), Wistar lineage, submitted to the removal of all whiskers from their right snout (vibrissectomy) since first day of life (P0) until the end of critical period of plasticity (P30). The 40 days deprived animals received epidural polimer implant of Elvax, previously saturated with chondroitinase ABC (ChABC, to degraded the extracellular matrix) or with bovine albumin serum(BSA, control), on the barrel cortex of contralateral cerebral hemisphere to the sensory deprivation (left). The animals were perfused 10 (P50) or 20 days (P60) after Elvax implant. Our results shown that the animals submitted to the sensory deprivation, during critical period of plasticity of S1, and to GAGsSC degradation presents modification in perineuronal net (PNNs) characteristics when compared to control animals, at P50. Those animals also presents increase in cFos labeled cells (mainly at the granular layer of S1) and in BDNF labeled cells at the deprived PMBSF, both seen in 10 (P50) as 20 days (P60) after Elvax implant saturated with ChABC. In this way, we concluded that GAGs-SC removal induced local plasticity, evoking changes in cortical activity and BDNF expression at the deprived PMBSF, even 30 days after critical period of plasticity ended at S1.
Acesso aberto (Open Access)
Avaliação dos efeitos no sistema nervoso central e estresse oxidativo do extrato hidroalcoólico de Petiveria alliacea L. (Phytolacaceae)
(Universidade Federal do Pará, 2011) ANDRADE, Thaís Montenegro de; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
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)
Efeito do metilmercúrio em girinos e recém-metamorfoseados de Physalaemos ephippifer (Steindachner, 1864) (Anura, Leptodactylidae)
(Universidade Federal do Pará, 2016-11-23) CASTELO BRANCO, Ailin; BAHIA, Verônica Regina Lobato de Oliveira; http://lattes.cnpq.br/1218901740124657; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649
The metal contamination in amphibians has been taken into account as one of the factors contributing to the population decline of these animals. The mercury (Hg) is an environmental contaminant showing high levels of toxicity. Its organic form, methylmercury (MeHg), may bioaccumulative reaching high levels in the trophic chain. For amphibian populations, bioaccumulation of metals is important once that such animals may be MeHg diffusers from the aquatic environment to the terrestrial environment because of their double life cycle. MeHg concentrations in high doses can cause obvious lethargic effects and larvae mortality of amphibious, however little is known about subchronic effects of MeHg doses. Therefore, the present research aims to explore the effects of subchronic exposure to MeHg in one experimental model, the species Physalaemus ephippifer, describing, identifying and characterizing the possible changes in physical performance of larvae and newly metamorphosed, in addition to teratogenic and morphological changes in the sensory and nervous system. After the toxicological test, with MeHg concentrations of 0.007 μg/ml, 0.004 μg/ml 0.0007 μg/ml and 0.0004 μg / ml and negative control, the animals were assessed by behavioral analysis simulating breakout predatory, morphometric and analysis in light microscopy and scanning electron microscopy. Our results revealed that MeHg concentrations did not induce locomotor weaknesses in tadpoles and nor apparent anatomical morphological damage, however, it induces the appearance of a massive cell count of pyknotic nuclei in the areas of the cerebellum and optic tectum. Such alteration, which remains in the animal even after metamorphosis, induces a locomotor weakness in concentration of 0,007μg/ml which is also the concentration where one increased teratogenic damage effect (corneal malformation) is observed. Therefore, we conclude that MeHg is a neurotoxic and teratogenic agent for P. ephippifer and that such features lead to one decrease in locomotor performance. The present work may contribute to the knowledge on effect of MeHg in amphibian populations that live in environments where this contaminant is present as member of the ecosystem.
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)
Estudo morfológico e imunológico da encefalite induzida pelo vírus juruaçá em modelo murino
(Universidade Federal do Pará, 2013-10-08) FERREIRA, Natalie Chaves; DINIZ JUNIOR, José Antônio Picanço; http://lattes.cnpq.br/1897655177251738
Many studies have been conducted to understand the neuropathogenesis of viral encephalitis from experimental work, however, no experimental studies have been devoted to understanding the neuropathogenesis of members of the Picornaviridae family isolated from bats in the Amazon region. The Juruaçá virus, one of these agents, partially characterized as a member of the Picornaviridae family by Araujo et al. (2006), caused lesions in the brain of neonatal mice with reactive gliosis presence, although not cause cytopathic effect (CPE) in primary cultures of central nervous system (CNS) cells, suggesting that this viral agent is responsible for the death of animals due to an intense immune response. The aim of this study was to investigate the immune response in the CNS and cellular changes caused by Juruaçá virus in newborn albino mice of strain BALB/c from histopathological analysis, microglial activation, and expression of cytokines, nitric oxide (NO) and reactive oxygen species (ROS). Thus, we performed sample processing for histopathology, immunosorbent assay, immunohistochemical and immunofluorescence assays, tests to quantify NO and superoxide radicals, and statistical analysis. Our results demonstrated that the Juruaçá virus induces lesions throughout the brain, with greater intensity in the cortical parenchyma. Immunohistochemical tests showed the presence of viral antigens and reactive microglias distributed throughout the brain and anterior spinal cord. Microglias with amoeboid shape, demonstrating intense activation, were observed in the cerebral cortex, olfactory bulb, anterior olfactory nucleus, midbrain and forebrain near the lateral ventricle. The production of anti-inflammatory cytokines (IL-10 and IL-4) decreased over time, whereas pro-inflammatory cytokines (IL -12, IL- 6, IL- 1β, TNF-α and IFN-γ) increased significantly from the 8th day. Assays for ROS detection showed great superoxide radicals production from the 4th day, as NO production was always lower in the infected animals. Probably, activation of glial cells, especially microglias, and subsequent production of proinflammatory cytokines and ROS promoted a devastating action on the cells of the CNS, which coincides with the intensification of clinical signs. In accordance with what has been explained above, became evident that our results indicate that the Juruaçá virus is responsible for a imprint inflammatory disease that leads to death 100% of infected neonates mice.
Acesso aberto (Open Access)
Exposição ao MEHG provoca dano na medula espinhal: percepções a partir da análise proteômica e estresse oxidativo
(Universidade Federal do Pará, 2020-08-27) EIRÓ, Luciana Guimarães; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/ 0000-0003-1486-4013
Methylmercury (MeHg) is considered by the World Health Organization as one of the chemicals of greatest public health concern. Thus, knowing the susceptibility of central nervous system regions and the absence of evidence about the effects on the spinal cord, this study aimed to investigate proteomic and biochemical changes in the spinal cord after MeHg long-term exposure at low doses. For this, male Wistar rats were exposed to a dose of 0.04 mg/kg/day by for 60 days. After that, the proteome was identified with subsequent overrepresentation analysis (ORA). For the oxidative biochemistry, the antioxidant (ACAP, TEAC, GSH) and pro-oxidants (LPO and nitrite ions) parameters were evaluated. The proteomic analysis showed several altered proteins that participate in biological processes, cellular components, and molecular functions. There was an increase in total mercury (Hg) levels in the spinal cord, as well as an increase in LPO and nitrite ions and a reduction in ACAP, TEAC and GSH. Therefore, exposure to low doses of MeHg can trigger oxidative stress associated with changes in the proteomic profile.
Acesso aberto (Open Access)
Imunopatologia experimental do vírus da raiva, com as variantes antigênicas 2 e 3
(Universidade Federal do Pará, 2015-06-02) CASSEB, Livia Medeiros Neves; VASCONCELOS, Pedro Fernando da Costa; http://lattes.cnpq.br/0973550817356564
The rabies is considered a zoonosis due have as host, reservoirs and transmitters the domestic or wild mammals. It´s characterized in acute disease caused by rabies virus (RABV) that affects the central nervous system (CNS) characterized by encephalitis with fatal prognosis in almost all cases, in any mammalian species. The aim of this study was to describe pathological findings and immunopathology of different strains of rabies virus in the tissues of the central nervous system, checking cellular and humoral immune response during experimental infection of Mus musculus mice. The animals were inoculated with two antigenic variants of RABV (VAg2 and VAg3), by different routes of infection, and a control group. The animals were observed for development of clinical signs and symptoms, collected and euthanized following a kinetic. The tissues were fixed in formaldehyde 10%, embedded in paraffin, stained with hematoxylin-eosin for histopathological analysis and with specific antibodies for immunohistochemical to characterize and quantify in situ distribution of the antigen and the inflammatory response. RABV antigens were found in the CNS in a diffuse way, but mainly in neurons. It was observed suppression of CD4+ lymphocytes, with increase of CD8+ lymphocytes. It was observed significant apoptosis with glial cell death and an increase of proinflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-1β and IL-8), anti-inflammatory (TGF-β and IL-4) and iNOS in both antigenic variants of RABV, but without observation of a TH17 profile. The analyses enable the characterization of rabies as meningoencephalitis, since it affects the meningeal, perivascular and intraparenchymal microenvironments. And the inflammatory process was observed even in the presence of inclusion bodies, but with less intensity.
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)
Investigação de tipos e origem celular neurogênicos em áreas diversas do sistema nervoso central da espécie Cebus apella
(Universidade Federal do Pará, 2015-07-27) SANTOS, Adriano Guimarães; HAMOY, Moisés; http://lattes.cnpq.br/4523340329253911; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Identifying populations of neuronal precursors and stem cells generated by own central nervous system has held discussions on its possible use in the repair of damage caused by acute disorders of the central nervous system. However, in the case of adult mammalian brain, such generation is considered evolutionarily restricted to two areas: subgranular zone of the dentate gyrus of the hippocampus, and the walls of the lateral ventricles where new neurons are continuously generated. We used 6 non-human primates, adults, males of the species Cebus (capuchin monkey, 10 years old), weighing between 2.1 and 2.8 kg (mean 2.5 kg) pretreated with BrdU that after sacrifice and because histological processing, their tissues were analyzed for immunohistochemical analysis using anti-BrdU anti-Nestin, and Sox2 anti-DCX in diverse areas of the Central Nervous System. The ventricular walls showed the presence of neuroblasts similar to that observed in previous studies, but unexpected results were also observed in areas such as the frontal cortex.
Acesso aberto (Open Access)
Neuropatologia experimental induzida pelos Rabdovírus Itacaiunas e Curionopolis: um estudo da resposta imune inata
(Universidade Federal do Pará, 2011-04-14) BARRETO, Leilane de Holanda; DINIZ JUNIOR, José Antônio Picanço; http://lattes.cnpq.br/3850460442622655
Experimental studies are making many efforts to understand the neuropathogenesis of viral encephalitis. However, a few is known about the Central Nervous System (CNS) response against amazonic rhabdovirus. The virus Itacaiunas e Curionopolis were classified preliminary as members of the Rhabdoviridae family. It was suggested for these virus to be included in a new genus, Bracorhabdovirus. They are neurotropic virus and little is known about the inflammatory response of the CNS against these virus. This study examined aspects of the immune response of newborn mice CNS resident cell after experimental infection by Itacaiunas and Curionopolis virus, in vivo and in vitro. To achieve these goals, histochemical and immunohistochemical techniques were used to detect activated microglia and astrocytes, respectively, in sections of the brains of infected mice. The quantification of these cells were performed in hippocampal regions using stereological techniques. Furthermore, was investigated the expression of proinflammatory and anti-inflammatory cytokines produced by CNS cells in primary cultures infected with virus Itacaiunas and Curionopolis by using enzyme immunoassay (ELISA) from supernatants co-cultures enriched of microglia/neurons and astrocytes/neurons. The expression of nitric oxide was also analyzed by using cytochemical reagent DAF-FM diacetate (4-amino-5-methylamine-2,7-difluorofluorescein-diacetate). As a result, age matched control animals of each group did not present activated microglia or astrocytosis, as well as, both Curionopolis and Itacaiunas infected subjects early after the inoculation (2d.a.i. and 4d.a.i respectively). However at 5th d.a.i., Curionopolis infections significant increase in the number of activated microglias and reactive astrocytes were detected whereas at the 7th d.a.i. after Itacaiunas infection only minimal activation of microglia and reactive astrocytosis was detected. The results from immunoassays showed great production of IL-12p40 in cultures of CNS cells infected with both virus, 48 and 96 hours after infection (h.a.i.). Low levels of TGF-β and IL-10 were detected after 48 hours of infection with both virus, however, was observed increased expression of this cytokines after 96 hours. CNS cell cultures infected with Curionopolis virus 48h.p.i. and Itacaiunas virus 48 and 96h.a.i. showed a slight production of nitric oxide, but it was increased in cultures infected with Curionopolis virus 96h.a.i. These results suggest that the proinflammatory response is dominant in both virus, however, it seems that the anti-inflammatory cytokines try to modulate the inflammatory response of the late days pos-inoculation.
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.
Acesso aberto (Open Access)
Potencial neuroprotetor da atividade física em populações ribeirinhas da Amazônia expostas ao mercúrio
(Universidade Federal do Pará, 2025-05) NAZARÉ, Caio Gustavo Leal de; OLIVEIRA, Marcus Augusto de; http://lattes.cnpq.br/6036530007649294; HTTPS://ORCID.ORG/0000-0002-4772-9929; LOPEZ, Maria Elena Crespo; http://lattes.cnpq.br/9900144256348265; https://orcid.org/0000-0002-1335-6853
Mercury is a highly toxic metal and is among the three substances with the greatest potential threat to human health. Its organic form, methylmercury, is particularly dangerous to human health due to its ability to easily cross biological barriers. The brain is a critical target for methylmercury, where it can cause neurological disorders, including motor, visual, auditory, behavioral, and cognitive deficits. Glial cells are closely involved in the mechanisms mediating such disorders and can either protect or damage the central nervous system (CNS), depending on the context. Moreover, no pharmacological treatment has proven effective against mercury intoxication to date, and literature has shown that both physical exercise and physical activity are capable of modulating glial aspects involved in the pathophysiology common to various neurological conditions and methylmercury intoxication. Thus, a potentially therapeutic and non-pharmacological approach, such as physical exercise – and even physical activity – would be particularly suitable for vulnerable populations who are economically, socially, and geographically disadvantaged, such as the riverine communities of the Amazon, who are chronically exposed to methylmercury through the consumption of contaminated fish. This study aims to assess whether physical activity profiles can influence the symptomatology of methylmercury intoxication in riverside residents of the Tucuruí Lake region. Interviews were conducted to obtain a profile of physical activity and self-reported neurological symptoms, and total mercury was measured from hair samples. Our results point to a possible and complex relationship between hair mercury levels and physical activity, suggesting that physical exercise may be a viable alternative to be included in daily life.
Acesso aberto (Open Access)
Ruptura do tendão calcâneo induz alterações bioquímicas e histológicas na medula espinhal de camundongos
(Universidade Federal do Pará, 2019-07-08) FRANÇA, Martha de Souza; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
The pathophysiology of the tendons involves release of neuronal mediators that play an active role in regulating tendon pain, inflammation and homeostasis. New directions have pointed out that injury is not restricted to tissue structural changes but indicates a possible involvement of the CNS in the regulation of the lesion. In this way, it is still unknown if the tendon injury affects the CNS, so the present study aims to investigate possible histological and biochemical changes in the spinal cord (L5) caused by the total rupture of the Achilles tendon in murine model. For this, the animals were submitted to tenotomy of the Achilles tendon, and separated in three groups (n = 36): Control; Rupture and Rupture+Suture. The total number cells of the spinal cord gray matter in the L5 vertebral segment was assessed by DAPI labeling. Glial reactivity was assessed by immunohistochemistry for microglia (IBA-1) and astrocytes (GFAP) at 7, 14 and 21 days after tendon rupture. The participation of the nitrergic system was investigated by the quantification of tissue levels of nitrite in lumbar intumescence at 7, 14 and 21 days post-injury and by iNOS (NOS2) immunostaining in L5. Statistical analyzes were performed using the ANOVA-1way test and post-test tukey, considering a significant p <0.05. The results were expressed as mean ± SD. The analysis of the number of cells showed that the Rupture group had a lower number of cells in 7 (1408.33 ± 58.59, p <0.05), 14 (1402.7 ± 72.7, p <0.05) and 21 (1374.5 ± 74.2, p <0.01) days post-injury in relation to the Control group (1668 ± 52.3) and in relation to the Rupture + Suture group on days 7 (1655 ± 66.5 , p <0.05) and 21 (1668.3 ± 14.1, p <0.01). The Suture group did not differ from the Control group. The results of glial reactivity showed that at 14 days after injury the microglia were activated at L5 and that astrocytes were activated at 7, 14 and 21 days after injury. The nitrite quantification showed higher levels of nitrite in the group Rupture in 7 (0.0004 ± 10.8x10-5, p <0.01) and 14 days (0.0006 ± 1.06 x10-5, p <0.01) post-injury in relation to the control group (0.0002 ± 3.45x10-5). Immunostaining for iNOS was identified at 14 days after injury in the Rupture group. Our results showed that the rupture of the Achilles tendon induces changes in the spinal cord in terms of total cell number, activation of glial cells and participation of the nitrergic system in a murine experimental model. In this way, it points to possible degenerative, oxidative, inflammatory and neural plasticity events in the spinal cord resulting from the Achilles tendon injury, highlighting the CNS participation in the repair process of this lesion.
Acesso aberto (Open Access)
Ruptura total do tendão de Aquiles induz resposta inflamatória e ativação glial na medula espinhal de camundongos
(Universidade Federal do Pará, 2022-05) PAULA, Diego Rodrigues de; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
Achilles tendon rupture is a common accident that affects both professional and recreational athletes. Acute and chronic pain are commonly seen in patients after rupture, usually associated with local inflammatory activation. The factors leading to hyperalgesia in symptomatic patients are poorly understood. Evidence suggests that Achilles tendon rupture is not restricted to tissue changes, but is able to evoke changes in the central nervous system (CNS). This study aimed to evaluate the impact of Achilles tendon rupture on the biochemical and histological profile in the spinal cord (L5) and on the nociceptive response in a murine model. The animals after Achilles tendon tenotomy surgery were divided into two groups: control (without rupture) and Rupture (tenotomized). Mechanical sensitivity test (von Frey) was assessed on the 7th and 14th day post-tenotomy (dpt). Glial reactivity was assessed by immunohistochemistry for microglia (IBA-1) and astrocytes (GFAP). Inflammatory activation was assessed by immunofluorescence for NOS-2 and COX2 at 7th and 14th dpt. We show, by the mechanical sensitivity test, an increase in the algesic response in the ipsilateral paw of the ruptured group on the 7th and 14th dpt when compared to the control group. This phenomenon was accompanied by hyperactivation of astrocytes and microglia in sensory processing areas of the L5 spinal cord, predominantly on the ipsilateral side to the tendon injury. We show inflammatory activation by expression of COX-2 and NOS-2, exclusively in the 14th dpt. These data were supported by biochemical findings that demonstrated significant nitrite levels increase in the lumbar spinal cord of animals submitted to Achilles tendon rupture at 7 and 14 dpt. The present study demonstrated for the first time that complete rupture of the Achilles tendon induces a neuroinflammatory response associated with glial activation in the spinal cord (L5) of mice.