Caracterização da resposta inflamatória e alterações neuroquímicas e eletrofisiológicas do tecido retiniano em modelo murino de malária cerebral induzido pela infecção por Plasmodium Berghei ANKA

Cerebral malaria (CM) is one of the most serious complications resulting from infection by P. falciparum and the leading cause of death in children. The CM frame has a complex pathogenesis associated with neurological complications arising in an enhanced immune response as well as hemorrhagic events. Studies describing retinopathy associated with the frame, together with an intense process of astrogliosis in the vicinity of retinal vessels that nourish the tissue. This paper sought to characterize the inflammatory process and the possible neurochemical and electrophysiological changes in the retinal tissue of Swiss albino mice, when inoculated with Plasmodium berghei ANKA strain (PbA). Swiss albino mice were infected with PbA strain. To characterize the above experimental cerebral malaria (ECM) was evaluated several parameters, such as onset of clinical signs, survival curves parasitemia (%) and body mass gain, vascular permeability and quantification of cytokines (TNF-α, IL-6 and IL-10) in the cortical tissue. To evaluate changes in retinal tissue functionality, use full-field electroretinography. For the evaluation of neurotransmitter systems release assay was performed and uptake of glutamate and GABA which was then quantified by High Performance Liquid Chromatography. The inflammatory response analysis was performed to quantify the cytokines (TNF-α, IL-6 and IL-10) in retinal tissue. After characterizing the MCE framework we observe a reduction in the amplitude of b-wave of rods and cones, as well as increase the implicit time of rods, mixed responses at different intensities and oscillatory potential. We observed an increase in the release and glutamate uptake and also the activation of an anti-inflammatory pathway in retinal tissue. This study allowed us to validate the murine model of MCE and characterize for the first time, changes in the retinal function accompanied by changes in the glutamatergic system as well as activation of the inflammatory pathway in retinal tissue.FAPESPA - Fundação Amazônia de Amparo a Estudos e PesquisasCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoA malária cerebral (MC) é uma das complicações mais graves resultante da infecção por P. falciparum e a principal causa de morte em crianças. O quadro de MC apresenta uma patogênese complexa, associado a complicações neurológicas provenientes de uma resposta imunológica exacerbada, bem como eventos hemorrágicos. Estudos descrevem uma retinopatia associada ao quadro, juntamente com um intenso processo de astrogliose nas proximidades de vasos que nutrem o tecido retiniano. O presente trabalho buscou caracterizar o processo inflamatório e as possíveis alterações neuroquímicas e eletrofisiológicas no tecido retiniano de camundongos albino suíço, quando inoculados com a cepa ANKA de Plasmodium berghei (PbA). Camundongos albino suíço foram infectados com cepa PbA. Para caracterização do quadro de malária cerebral experimental (MCE) foram avaliados diversos parâmetros, como surgimento dos sinais clínicos, curva de sobrevivência, parasitemia (%), ganho de massa corpórea, permeabilidade vascular e quantificação de citocinas (TNF-α, IL-6 e IL-10) no tecido cortical. Para avaliarmos alterações na funcionalidade do tecido retiniano, utilizamos eletrorretinograma de campo total. Para a avaliação dos sistemas de neurotransmissão foi realizado ensaio de liberação e captação de glutamato e GABA que, posteriormente foi quantificado por Cromatografia Líquida de Alta Eficiência. Para análise da resposta inflamatória foi realizada a quantificação de citocinas (TNF-α, IL-6 e IL-10) no tecido retiniano. Após a caracterização do quadro de MCE nós observamos a diminuição da amplitude de onda-b de cones e bastonetes, bem como aumento do tempo implícito de bastonetes, respostas mistas em diferentes intensidades e potencial oscilatório. Observamos aumento na liberação e captação de glutamato e, ainda, a ativação de uma via antiinflamatória no tecido retiniano. Este trabalho nos permitiu validar o modelo murino de MCE e caracterizar, pela primeira vez, alterações na funcionalidade do tecido retiniano, acompanhada de alterações no sistema glutamatérgico, bem como ativação de uma via antiinflamatória no tecido retiniano

Exposição subcrônica de ratos wistar jovens a dose baixa de chumbo induz déficits locomotores e alterações morfológicas associados a estresse oxidativo e disfunção sináptica

Lead (PB) is a heavy metal, which can be utilized in the production of several compounds. The main route of human exposure is through the consumption of contaminated food or water, and once absorbed, about 99% of the circulating lead spreads to soft tissues, teeth, bones and brain. In the Central nervous system (CNS), several studies have demonstrated deficits in learning capacity, cognition and intellectual development in humans exposed to lead during a given period of life. However, it is poorly understood the mechanisms of action involved with the toxicity of Pb. From this, this study aimed to evaluate the exploratory, motor and tissue effects induced by the subchronic exposure of young wistar rats to 50 mg/Kg of lead, associated with possible mechanisms of action. Male Wistar rats were exposed for 55 days at a dose of 50mg/Kg of Pb per gavage, and the control animals received distilled water. The open field, inclined plane and route-rod tests were performed for locomotor evaluation. Staining was performed with Hematoxylin and Eosin, as well as immunohistochemistry for the quantification of mature neurons, myelin sheath and synaptic vesicles. To evaluate the protein expression, the Proteomic profile was performed. The statistical analysis was performed by Student's T-Test, being considered significant p < 0.05. After we observed lead deposition only in the cerebellum, it was possible to characterize exploratory and motor deficits in the rats exposed to lead, and we observed a decrease in the number of Purkinje cells, as well as mature neurons, reduction of vesicles synaptic and decreased myelin sheath. In the evaluation of oxidative stress induction, it was possible to evaluate the increase of MDA and nitrite only in the motor cortex. And in the evaluation of protein expression, both regions presented alterations in proteins responsible for the release process of neurotransmitters, as well as receptors and second messengers, and also proteins involved in the process of apoptose. Thus, we conclude that the subchronic exposure to low Pb dose of young Wistar rats promoted locomotor and histological tracings, associated with induction of oxidative stress, alterations in the process of cell signaling, as well as death by apoptosis.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorO chumbo (Pb) é um metal pesado, que pode ser utillizado na produção de diversos compostos. A principal via de exposição do homem é através do consumo de comida ou água contaminada, sendo que uma vez absorvido, cerca de 99% do chumbo circulante difunde-se para tecidos moles, dentes, ossos e cérebro. No Sistema Nervoso Central (SNC), diversos estudos vêm demonstrando déficits na capacidade de aprendizagem, cognição e desenvolvimento intelectual em humanos expostos ao chumbo durante determinado período da vida. Contudo, encontra-se pouco compreendido os mecanismos de ação envolvidos com a toxicidade do Pb. A partir disso, este estudo buscou avaliar os efeitos exploratórios, motores e teciduais induzidos pela exposição subcrônica de ratos Wistar jovens a 50 mg/Kg de chumbo, associado a possíveis mecanismos de ação. Foram utilizados ratos machos Wistar, expostos durante 55 dias a uma dose de 50mg/Kg de Pb por gavagem, sendo que os animais controles receberam água destilada. Realizou-se os testes de campo aberto, plano inclinado e rota-rod para avaliação locomotora. Foi realizado coloração com hematoxilina e eosina, bem como, imuno-histoquímica para quantificação de neurônios maduros, bainha de mielina e vesículas sinápticas. Para avaliação da expressão de proteínas foi realizado o perfil proteômico. A análise estatística foi realizada pelo teste t de Student, sendo considerado como significativo p <0,05. Após observamos depósito de chumbo apenas no cerebelo, foi possível caracterizar déficits exploratórios e motores nos ratos expostos ao chumbo, sendo que observamos diminuição no número de células de Purkinje, bem como neurônios maduros, diminuição de vesículas sinápticas e diminuição da bainha de mielina. Na avaliação da indução de estresse oxidativo, foi possível avaliar aumento de MDA e nitrito apenas no córtex motor. E na avaliação da expressão de proteínas, ambas as regiões apresentaram alterações em proteínas responsáveis pelo processo de liberação de neurotransmissores, bem como receptores e segundos mensageiros e, ainda, proteínas envolvidas com processo de apoptose. Com isso, concluímos que o a exposição subcrônica a baixa dose de Pb de ratos Wistar jovens promoveu altrações locomotoras e histológicas, associado a indução de estresse oxidativo, alterações no processo de sinalização celular, bem como morte por apoptose

Effects of exposure to aluminum citrate in a model of induced alveolar bone loss in rats

282-287Aluminum (Al) is the most abundant metal in the earth's crust and is found naturally in the air, water, and soil. Al may pose a major threat to humans, causing diseases and bone disorders. Nevertheless, the effects of Al on alveolar bone are not reported in the literature. Here, we investigated the effects of sub-chronic intoxication with Al citrate in a model of alveolar bone loss, induced by ligature, in male Wistar rats. The animals were exposed to Al citrate (100 mg/kg/day), by gavage, for 30 days. We used 40 rats equally divided into four groups: Control; Experimental Periodontitis (EPeriodontitis); Al; Al+EPeriodontitis. After exposure period, we evaluated the concentration of Al in the blood and alveolar bone, as well as the Al measurement in alveolar bone. The results showed that the Al exposure promoted distribution of Al in blood serum and in the alveolar bone. The Al exposure per si results in alveolar bone loss as well as potentiates damages of periodontitis induced cases. These results suggest that levels aluminum in the blood and alveolar bone induce alveolar bone loss, besides present aggravating effect in the presence of induced periodontitis

Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats

Lead (Pb) is an environmental contaminant that presents a high risk for human health. We aimed to investigate the possible alterations triggered by the exposure to Pb acetate for a long period in motor performance and the possible relationship with biochemical, proteomic and morphological alterations in the cerebellum of rats. Male Wistar rats were exposed for 55 days, at 50 mg/Kg of Pb acetate, and the control animals received distilled water. Open field (OF) and rotarod tests; biochemistry parameters (MDA and nitrite); staining/immunostaining of Purkinje cells (PC), mature neurons (MN), myelin sheath (MS) and synaptic vesicles (SYN) and proteomic profile were analyzed. Pb deposition on the cerebellum area and this study drove to exploratory and locomotion deficits and a decrease in the number of PC, MN, SYN and MS staining/immunostaining. The levels of MDA and nitrite remained unchanged. The proteomic profile showed alterations in proteins responsible for neurotransmitters release, as well as receptor function and second messengers signaling, and also proteins involved in the process of apoptosis. Thus, we conclude that the long-term exposure to low Pb dose promoted locomotion and histological tracings, associated with alterations in the process of cell signaling, as well as death by apoptosis

Non-mammalian models in behavioral neuroscience: Consequences for biological psychiatry

Current models in biological psychiatry focus on a handful of model species, and the majority of work relies on data generated in rodents. However, in the same sense that a comparative approach to neuroanatomy allows for the idenfication of patterns of brain organization, the inclusion of other species and an adoption of comparative viewpoints in behavioral neuroscience could also lead to increases in knowledge relevant to biological psychiatry. Specifically, this approach could help to identify conserved features of brain structure and behavior, as well as to understand how variation in gene expression or developmental trajectories relates to variation in brain and behavior pertinent to psychiatric disorders. To achieve this goal, the current focus on mammalian species must be expanded to include other species, including non-mammalian taxa. In this article, we review behavioral neuroscientific experiments in non-mammalian species, including traditional 'model organisms' (zebrafish, Drosophila and C. elegans) as well as in other species which can be used as 'reference'. The application of these domains in biological psychiatry and their translational relevance is considered