Inflammatory Effects of Highly Pathogenic H5N1 Influenza Virus Infection in the CNS of Mice

Department of Developmental Neurobiology, Division of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 02/2012; 32(5):1545-59. DOI: 10.1523/JNEUROSCI.5123-11.2012
Source: PubMed

ABSTRACT The A/VN/1203/04 strain of the 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 neurons located in the substantia nigra pars compacta (SNpc), expression of monoamines 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 dopaminergic phenotype in SNpc and now report that this loss recovers by 90 d after infection. 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 d after infection. In each of these brain regions, we found a significant increase in the number of activated microglia that lasted at least 90 d. 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, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, eotaxin, interferon-inducible protein 10, cytokine-induced neutrophil chemoattractant, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP) 1α, MIP-1β, and VEGF, and found 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.

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Available from: Richard J Smeyne, Sep 29, 2015
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    • "on dry ice, ventral side up. Two-millimeter coronal slices 243 including the SN were isolated using anatomical 244 landmarks for the midbrain/SN (Jang et al., 2012) and 245 placed immediately in Eppendorf tubes in dry ice. "
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    • "In addition, we observed severe gliosis, which was possibly due to neuronal death in the infected brain. These findings support previous reports suggesting that influenza A virus induces severe neuroinflammation in the brain accompanied by gliosis [24,42,43]. "
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    Veterinary Research 06/2014; 45(1):63. DOI:10.1186/1297-9716-45-63 · 2.82 Impact Factor
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    • "It is interesting that in this study, the mouse strains that had lower levels of ADO are those that are generally more sensitive to xenobiotic agents used in modeling of Parkinson’s disease, including MPTP and paraquat [81]–[84]. Given that recent studies have shown that dopamine can act as an inflammatory molecule in the brain [85] and that excess levels of dopamine can readily autoxidize to form free radicals [86], it is possible that differing levels of ADO pools may play a role in how dopamine is modulated an thus those individuals or animals with higher pools of basal ganglia ADO may be less prone to developing Parkinson’s disease [87], [88]. "
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