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Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice

Molecular Psychiatry volume 10, pages 299–308 (2005)Cite this article

Abstract

Epidemiological studies have indicated a link between certain neuropsychiatric diseases and exposure to viral infections. In order to examine long-term effects on behavior and gene expression in the brain of one candidate virus, we have used a model involving olfactory bulb injection of the neuro-adapted influenza A virus strain, WSN/33, in C57Bl/6 mice. Following this olfactory route of invasion, the virus targets neurons in the medial habenular, midline thalamic and hypothalamic nuclei as well as monoaminergic neurons in the brainstem. The mice survive and the viral infection is cleared from the brain within 12 days. When tested 14–20 weeks after infection, the mice displayed decreased anxiety in the elevated plus-maze and impaired spatial learning in the Morris water maze test. Elevated transcriptional activity of two genes encoding synaptic regulatory proteins, regulator of G-protein signaling 4 and calcium/calmodulin-dependent protein kinase IIα, was found in the amygdala, hypothalamus and cerebellum. It is of particular interest that the gene encoding RGS4, which has been related to schizophrenia, showed the most pronounced alteration. This study indicates that a transient influenza virus infection can cause persistent changes in emotional and cognitive functions as well as alterations in the expression of genes involved in the regulation of synaptic activities.

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Acknowledgements

This study was supported by grants from the Stanley Medical Research Institute, the Swedish Research Council (04480 and 11588) and Stiftelserna Sigurd och Elsa Goljes minne, Ragnhild och Einar Lundströms minne, AlzheimerFonden and Wallenberg Consortium North. F Aronsson is the recipient of a scholarship from the ‘Network for Inflammation Research’ funded by the Swedish Foundation for Strategic Research.

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Authors and Affiliations

  1. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    S Beraki, F Aronsson, H Karlsson, S O Ögren & K Kristensson

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  1. S Beraki
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  4. S O Ögren
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Correspondence to S O Ögren.

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Beraki, S., Aronsson, F., Karlsson, H. et al. Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice. Mol Psychiatry 10, 299–308 (2005). https://doi.org/10.1038/sj.mp.4001545

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