Abstract
Schizophrenia is a major debilitating disease with a lifetime prevalence of 1% throughout the world. There is robust epidemiologic evidence indicating that environmental contributions, such as prenatal infections, may lead to the genesis of schizophrenia. Our laboratory has developed an animal model using human influenza virus to infect pregnant Balb/c and C57BL/6 mice intranasally at selected time points during pregnancy to investigate the role of prenatal viral infection on brain development. In this chapter, we review our research using this model and the changes in brain structure, gene expression, neurochemistry, and behavior that are observed in the offspring of infected dams. Our observations are consistent with findings observed in subjects with schizophrenia, providing additional evidence for the role of prenatal viral infection in the etiology of this disease.
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Acknowledgments
Grant support by National Institute of Child Health and Human Development (#5R01-HD046589-04 and 3R01-HD046589-04S1) to SHF is gratefully acknowledged. Portions of this article are reprinted from: (1) Fatemi, S. H., Folsom, T. D., Reutiman, T. J., Abu-Odeh, D., Mori, S., Huang, H., et al. (2009). Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice. Schizophr Res, 112(1–3), Copyright (2009), with permission from Elsevier; (2) Fatemi, S. H., Folsom, T. D., Reutiman, T. J., Huang, H., Oishi, K., & Mori, S. (2009). Prenatal viral infection of mice at E16 causes changes in gene expression in hippocampi of the offspring. Eur Neuropsychopharmacol, 19(9), Copyright (2009), with permission from Elsevier; (3) Fatemi, S. H., Folsom, T. D., Reutiman, T. J., Huang, H., Oishi, K., Mori, S., et al. (2008). Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders. Schizophr Res, 99(1–3), Copyright (2008), with permission from Elsevier; (4) with kind permission from Springer Science+Business Media: Fatemi, S. H., Reutiman, T. J., Folsom, T. D., & Sidwell, R. W. (2008). The role of cerebellar genes in pathology of autism and schizophrenia. Cerebellum, 7; and (5) Fatemi, S. H., Folsom, T. D., Reutiman, T. J., & Sidwell, R. W. (2009). Viral regulation of aquaporin 4, connexin 43, microcephalin, and nucleolin. Schizophr Res, 98(1–3), Copyright (2009), with permission from Elsevier.
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Fatemi, S.H., Folsom, T.D. (2011). Prenatal Viral Infection in Mouse: An Animal Model of Schizophrenia. In: Clelland, J. (eds) Genomics, Proteomics, and the Nervous System. Advances in Neurobiology, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7197-5_4
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