RESUMO
Dengue virus is a human pathogen that may cause meningoencephalitis and other neurological syndromes. The current study investigated anxiety-like behavior and expression of proinflammatory cytokines and pro-apoptotic caspase-3 in the hippocampus of C57BL/6 mice infected with non-adapted Dengue virus 3 genotype I (DENV-3) inoculated intracranially with 4×10(3) (plaque-forming unit) PFU. Anxiety-like behavior was assessed in control and DENV-3 infected mice using the elevated plus maze. The open field test was performed to evaluate locomotor activity. Histopathological changes in CA regions of the hippocampus were assessed by haematoxylin and eosin staining. Immunoreactive and protein levels of cleaved caspase-3 were also analyzed in the hippocampus. The mRNA expression of IL-6 and TNF-α in the hippocampus were estimated by quantitative real time (polymerase chain reaction) PCR. All procedures were conducted on day 5 post-infection. We found that DENV-3 infected mice presented higher levels of anxiety in comparison with controls (p≤0.05). No difference in motor activity was found between groups (p=0.77). The infection was followed by a significant increase of TNF-α and IL-6 mRNA expression in the hippocampus (p≤0.05). Histological analysis demonstrated meningoencephalitis with formation of perivascular cuffs, infiltration of immune cells and loss of neurons at CA regions of hippocampus. Numerous caspase-3 positive neurons were visualized at CA areas in DENV-3 infected mice. Marked increase of cleaved caspase-3 levels were observed after infection. This study described anxiety-like behavior, hippocampal inflammation and neuronal apoptosis associated with DENV-3 infection in the central nervous system.
Assuntos
Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/virologia , Dengue/complicações , Encefalite/complicações , Encefalite/etiologia , Animais , Apoptose/fisiologia , Vírus da Dengue/genética , Vírus da Dengue/patogenicidade , Vírus da Dengue/fisiologia , Modelos Animais de Doenças , Encefalite/patologia , Comportamento Exploratório/fisiologia , Hipocampo/metabolismo , Hipocampo/virologia , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Experimental cerebral malaria is a neuroinflammatory condition that results from the host immune response to the parasite. Using intravital microscopy, we investigated leukocyte recruitment in the brain microcirculation and the temporal relationship of this process to the behavioral changes observed in Plasmodium berghei (strain ANKA)-infected C57Bl/6 mice. We found that leukocyte recruitment was increased from day 5 post-infection (p.i.) onwards. Histopathological changes and increased levels of inflammatory cytokines in the brain were also observed. Behavioral performance evaluated by the SHIRPA protocol showed functional impairment from day 6 p.i. onwards. Thus, early leukocyte migration into the brain and associated inflammatory changes may be involved in neurological impairment in parasite-infected C57Bl/6 mice.
