Navegando por Autor "GOMES, Giovanni Freitas"

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Acesso aberto (Open Access)
Alterações da morfologia da micróglia do septo lateral e comportamento semelhante ao ansioso em um modelo murino de inoculação sequencial de VDEN1 e VDEN4: influência do enriquecimento ambiental
(Universidade Federal do Pará, 2016-05-05) GOMES, Giovanni Freitas; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286; SÓSTHENES, Márcia Consentino Kronka; http://lattes.cnpq.br/7881527576747420
Dengue disease is the major cause of deaths by arbovirus infections in Brazil. In the American Continent, the epidemics seem to be associated to the fact that multiple dengue virus (VDEN) serotypes circulate simultaneously. Despite its epidemiological importance and a century of systematic studies dedicated to understand the disease, its detailed pathogenic mechanisms remain poorly understood. The objective of this study was to evaluate possible influence of environmental enrichment on behavioral changes and microglial morphology alterations in the lateral septum after sequential VDEN1 and VDEN4 intraperitoneal inoculations of infected brain homogenates. To that end, we used adult females ten months old of an immunocompetent albino Swiss mouse strain housed in standard or enriched cages. A single intraperitoneal infection of VDEN1 was followed after 28 days by another inoculation of VDEN4. To enhance clinical signs, a regimen of daily alternated injections of VDEN1 or VDEN4 followed 24 hours later by anti-VDEN2 antibody was applied in the last 7 days. Control animals received equal volumes and regime of inoculation of uninfected brain homogenate. We assessed the behavioral changes using the open field exploratory (OF) and elevated plus-maze (EPM). Infected animals housed in standard cages showed significant decrease in time of exploration of the periphery in the OF and in the time of exploration of enclosed arm in the EPM. Uninfected mice housed in standard cages and animal housed in enriched cages did not show same changes. To check how possible microglial changes could be influenced by acute DENV1 infection, secondary DENV4 infection or the passive anti-DENV4 inoculation, we decided to sacrifice groups of animals after which point of inoculation. To evaluate microglial changes, we did selective immunohistochemistry for microglia and macrophages using anti-IBA-1 antibody (Wako, Japan) and we used tri-dimensional reconstruction to morphometric evaluation. Compared to uninfected, infected mice from standard cages showed significant changes in microglial morphology. We also tested the hypothesis that septal microglia is clustered in subtypes and that DENV infection could change this pattern. We noticed microglia is subdivided in three subgroups in physiological conditions, a more complex pattern, a less complex pattern and an intermediate. After DENV1 or DENV4 infection, we observed changes in this pattern, including the appearance of a high complexity cell, increasing the percentage of complexes microglia. We observed these changes in animals from standard cages, but not in animals from enriched cages. Another interesting data is that environmental enrichment appears to reduce this morphometric changes. Based on the evidences, we suggest that sequential infection with VDEN1/VDEN4 in murine model induced behavioral changes and microglial changes in the lateral septum and EA appears to protect animals against these alterations. Based on these evidences, we suggest that microglial from lateral septum present a heterogeneous pattern of morphology and that DENV infection can induce morphological changes, and alterations in the pattern of subdivision, associated with the increase in the percentage of high complexity cells. In addition, infection can induces behavioral changes detected by EPM and OF tests and environmental enrichment seems to protect against microglial and behavioral changes.
Acesso aberto (Open Access)
Environmental influences on antibody-enhanced dengue disease outcomes
(2012-12) DINIZ, Daniel Guerreiro; FÔRO, César Augusto Raiol; TURIEL, Maíra Catherine Pereira; SÓSTHENES, Márcia Consentino Kronka; DEMACHKI, Samia; GOMES, Giovanni Freitas; REGO, Carla M Damasceno; MAGALHÃES, Marina Cutrim; PINHO, Brunno Gomes; RAMOS, Juliana Pastana; CASSEB, Samir Mansour Moraes; BRITO, Maysa de Vasconcelos; SILVA, Eliana Vieira Pinto da; NUNES, Márcio Roberto Teixeira; DINIZ JUNIOR, José Antônio Picanço; CUNNINGHAM, Colm; PERRY, Victor Hugh; VASCONCELOS, Pedro Fernando da Costa; DINIZ, Cristovam Wanderley Picanço
Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lymphocytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE.