Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice.
Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice.
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DOI：
10.1523/jneurosci.5123-11.2012
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发表时间：
2012-02-01
期刊：
影响因子：
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通讯作者：
Smeyne RJ
中科院分区：
文献类型：
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作者：
Jang H;Boltz D;McClaren J;Pani AK;Smeyne M;Korff A;Webster R;Smeyne RJ
A/VN/1203/04型H5N1流感病毒能够感染小鼠中枢神经系统并诱发多种神经退行性病理。在这里，我们研究了H5N1对帕金森病的几个病理方面的影响，包括位于黑质致密部（SNpc）的多巴胺能（DAergic）神经元表型的丧失，大脑中单胺和吲哚胺的表达，SNpc小胶质细胞数量和形态的改变，以及细胞因子、趋化因子和生长因子的表达。我们发现H5N1诱导SNpc中DAergic表型的短暂丧失，现在报告这种丧失在感染后90天恢复（dpi）。在基底神经节的单胺水平中也可以看到类似的损失和恢复模式。在3dpi、10dpi、2dpi、60dpi和90dpi时检查肺和已知为H5N1病毒靶点的大脑不同区域（脑干、黑质、纹状体和皮层）的炎症反应。我们发现，在这些大脑区域中，激活的小胶质细胞数量显著增加，这种情况持续了至少90天。我们还量化了IL-1α、IL-1β、IL-2、IL-6、IL-9、IL-10、IL-12（p70）、IL-13、TNF-α、IFN-γ、GM-CSF、G-CSF、M-CSF、eotaxin、IP-10、KC、MCP-1、MIP-1α、MIP-1β和VEGF的表达，发现表达模式和水平与感染后的脑区域和时间有关。我们得出结论，小鼠的H5N1感染在大脑中诱导了持久的炎症反应，并可能在神经退行性疾病的病理发展中发挥作用。
The A/VN/1203/04 H5N1 influenza virus is capable of infecting the CNS of mice and inducing a number of neurodegenerative pathologies. Here, we examined the effects of H5N1 on several pathological aspects affected in parkinsonism, including loss of the phenotype of dopaminergic (DAergic) neurons located in the substantia nigra pars compacta (SNpc), expression of mono- and indolamines in brain, alterations in SNpc microglia number and morphology, and expression of cytokines, chemokines and growth factors. We find that H5N1 induces a transient loss of the DAergic phenotype in SNpc and now report that this loss recovers by 90 days post infection (dpi). A similar pattern of loss and recovery was seen in monoamine levels of the basal ganglia. The inflammatory response in lung and different regions of the brain known to be targets of the H5N1 virus (brainstem, substantia nigra, striatum, and cortex) were examined at 3, 10, 21, 60 and 90 dpi. We found a significant increase in the number of activated microglia in each of these brain regions that lasted at least 90 days. We also quantified expression of IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-12(p70), IL-13, TNF-α, IFN-γ, GM-CSF, G-CSF, M-CSF, eotaxin, IP-10, KC, MCP-1, MIP-1α, MIP-1β and VEGF and find that the pattern and levels of expression are dependent on both brain region and time after infection. We conclude that H5N1 infection in mice induces a long-lasting inflammatory response in brain and may play a contributing factor in the development of pathologies in neurodegenerative disorders.