title: Dengue-3 encephalitis promotes anxiety-like behavior in mice.
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.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Aline Silva
authors.initials: AS
authors.lastname: de Miranda
authors.forename: David Henrique
authors.initials: DH
authors.lastname: Rodrigues
authors.forename: Débora Cristina Guerra
authors.initials: DC
authors.lastname: Amaral
authors.forename: Roberta Dayrell
authors.initials: RD
authors.lastname: de Lima Campos
authors.forename: Daniel
authors.initials: D
authors.lastname: Cisalpino
authors.forename: Márcia Carvalho
authors.initials: MC
authors.lastname: Vilela
authors.forename: Norinne
authors.initials: N
authors.lastname: Lacerda-Queiroz
authors.forename: Kátia Paulino Ribeiro
authors.initials: KP
authors.lastname: de Souza
authors.forename: Juliana Priscila
authors.initials: JP
authors.lastname: Vago
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: Campos
authors.forename: Erna Geesien
authors.initials: EG
authors.lastname: Kroon
authors.forename: Danielle
authors.initials: D
authors.lastname: da Glória de Souza
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.forename: Milene Alvarenga
authors.initials: MA
authors.lastname: Rachid
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000209:etiology* / Q000821:virology*; D017209:Apoptosis / Q000502:physiology; D003715:Dengue / Q000150:complications*; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000150:complications* / Q000209:etiology* / Q000473:pathology; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000821:virology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins