Development

A viral model for mental illness based on a known risk factor

Limin Shi, Paul H. Patterson

Epidemiological studies have shown that maternal infection can increase the risk for mental illness in the offspring. In a mouse model of maternal respiratory infection with influenza virus, the adult offspring display striking behavioral, pharmacological and histological abnormalities. Using RT-PCR assays for four viral genes, we find no evidence of viral infection of the fetal brain. This supports our earlier evidence that it is the mother’s immune response to infection, rather than viral infection of the fetus, that is key to altering fetal brain development. Pathology studies have shown a number of abnormalities in prefrontal cortex, hippocampus and cerebellum of patients with autism and schizophrenia. Using immunohistochemistry and in situ hybridization, we are characterizing various changes in the brains of the offspring of infected mothers. at several development stages.

Do cytokines mediate the effects of maternal viral infection on fetal brain development?

Stephen Smith, Jennifer Li, Paul H. Patterson

Human studies demonstrate an increased risk for both schizophrenia and autism in children born to mothers who experienced a viral infection during pregnancy. We are exploring a mouse model in which administration of influenza virus during pregnancy induces behavioral abnormalities in the adult offspring. As no virus is found in the fetal brain, and immune stimulation by LPS or poly(I:C) is sufficient to cause behavioral abnormalities in the offspring, we hypothesize that the maternal immune response to infection alters fetal brain development and results in abnormal adult behavior. We are attempting to mimic the effects of maternal infection with administration of poly(I:C) or individual cytokines to determine which components of the immune response are most detrimental to fetal development. We are also testing the effects of maternal injection of anti-cytokine antibodies along with poly(I:C) in pregnant mice, and identifying vulnerable cells expressing cytokine receptors in the fetus. Another project involves the study of inflammatory cells in the fetuses of infected or poly(I:C)-injected mothers.






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