Departamento de Clínica Médica, Faculdade de Medicina, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Behav Brain Res. 2012 Apr 21;230(1):237-42. doi: 10.1016/j.bbr.2012.02.020. Epub 2012 Feb 17.
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.
登革病毒是一种人类病原体，可能导致脑膜脑炎和其他神经综合征。本研究调查了非适应型登革病毒 3 型 I（DENV-3）感染的 C57BL/6 小鼠颅内接种 4×10(3)（噬菌斑形成单位）PFU 后，焦虑样行为以及海马中促炎细胞因子和促凋亡半胱天冬酶-3 的表达。使用高架十字迷宫评估对照和 DENV-3 感染小鼠的焦虑样行为。通过旷场试验评估运动活动。通过苏木精和伊红染色评估海马 CA 区的组织病理学变化。还分析了海马中裂解的半胱天冬酶-3 的免疫反应性和蛋白水平。通过定量实时（聚合酶链反应）PCR 估计海马中 IL-6 和 TNF-α 的 mRNA 表达。所有程序均在感染后第 5 天进行。我们发现，与对照组相比，DENV-3 感染的小鼠表现出更高水平的焦虑（p≤0.05）。两组之间的运动活动没有差异（p=0.77）。感染后，海马中 TNF-α 和 IL-6 mRNA 表达显著增加（p≤0.05）。组织学分析显示脑膜脑炎，伴有血管周围套形成、免疫细胞浸润和海马 CA 区神经元丢失。在 DENV-3 感染的小鼠中，CA 区可见大量 caspase-3 阳性神经元。感染后观察到裂解的 caspase-3 水平明显增加。本研究描述了与 DENV-3 感染相关的中枢神经系统中的焦虑样行为、海马炎症和神经元凋亡。
