Article
Dengue-3 encephalitis promotes anxiety-like behavior in mice
Registro en:
MIRANDA, Aline Silva de et al. Dengue-3 encephalitis promotes anxiety-like behavior in mice. Behavioural Brain Research. 2012, vol.230, n. 1, p. 237-242
0166-4328
10.1016/j.bbr.2012.02.020.
Autor
Miranda, Aline Silva de
Rodrigues, David Henrique
Amaral, Débora Cristina Guerra
Campos, Roberta Dayrell de Lima
Cisalpino, Daniel
Vilela, Márcia Carvalho
Queiroz, Norinne Lacerda
Souza, Kátia Paulino Ribeiro de
Vago, Juliana Priscila
Campos, Marco Antônio
Kroon, Erna Geesien
Souza, Danielle da Glória de
Teixeira, Mauro Martins
Teixeira, Antônio Lúcio
Rachid, Milene Alvarenga
Resumen
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 × 103 (plaque-forming unit) PFU. Anxiety-like behavior was assessedincontrol and DENV-3 infectedmiceusing the elevatedplusmaze. 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- 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- 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 anxietylike behavior, hippocampal inflammation and neuronal apoptosis associated with DENV-3 infection in the central nervous system.