Dengue-3 encephalitis promotes anxiety-like behavior in mice

Aline Silva de Miranda, David Henrique Rodrigues, Débora Cristina Guerra Amaral, Roberta Dayrell de Lima Campos, Daniel Cisalpino, Márcia Carvalho Vilela, Norinne Lacerda-Queiroz, Kátia Paulino Ribeiro de Souza, Juliana Priscila Vago, Marco Antônio Campos, Erna Geesien Kroon, Danielle da Glória de Souza, Mauro Martins Teixeira, Antônio Lúcio Teixeira, Milene Alvarenga Rachid

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)237-242
Number of pages6
JournalBehavioural Brain Research
Volume230
Issue number1
DOIs
StatePublished - Apr 21 2012
Externally publishedYes

Keywords

  • Anxiety-like behavior
  • Elevated plus maze
  • Hippocampus
  • Inflammation
  • Non-adapted DENV-3

ASJC Scopus subject areas

  • Behavioral Neuroscience

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