TY - JOUR
T1 - Dengue-3 encephalitis promotes anxiety-like behavior in mice
AU - de Miranda, Aline Silva
AU - Rodrigues, David Henrique
AU - Amaral, Débora Cristina Guerra
AU - de Lima Campos, Roberta Dayrell
AU - Cisalpino, Daniel
AU - Vilela, Márcia Carvalho
AU - Lacerda-Queiroz, Norinne
AU - de Souza, Kátia Paulino Ribeiro
AU - Vago, Juliana Priscila
AU - Campos, Marco Antônio
AU - Kroon, Erna Geesien
AU - da Glória de Souza, Danielle
AU - Teixeira, Mauro Martins
AU - Teixeira, Antônio Lúcio
AU - Rachid, Milene Alvarenga
PY - 2012/4/21
Y1 - 2012/4/21
N2 - 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.
AB - 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.
KW - Anxiety-like behavior
KW - Elevated plus maze
KW - Hippocampus
KW - Inflammation
KW - Non-adapted DENV-3
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UR - http://www.scopus.com/inward/citedby.url?scp=84857756717&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2012.02.020
DO - 10.1016/j.bbr.2012.02.020
M3 - Article
C2 - 22366269
AN - SCOPUS:84857756717
SN - 0166-4328
VL - 230
SP - 237
EP - 242
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -