Prenatal Infections and Long-term Mental Outcome: Modeling Schizophrenia-related Dysfunctions Using the Prenatal PolyI:C Model in Mice
Joram Feldon
Joram Feldon, The Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich (ETH), SWITZERLAND
Abstract:
Based on the epidemiological association between maternal infection during pregnancy and enhanced risk of neurodevelopmental brain disorders in the offspring, a number of in-vivo models have been established in rats and mice in order to study this link on an experimental basis. One such model is based on prenatal exposure to the viral mimic polyriboinosinic-polyribocytidilic acid (PolyI:C) in mice. This model has proven to be an excellent experimental tool to study the contribution of immune-mediated neurodevelopmental disturbances to complex behavioral and cognitive functions which are especially known to be disrupted in schizophrenia and related psychotic disturbances. Since its initial establishment, the PolyI:C model has made a great impact on researchers concentrating on the neurodevelopmental and neuroimmunological basis of complex human brain disorders such as schizophrenia, and as a consequence, the model now enjoys wide recognition in the international scientific community. Here, I shall summarize the features and methodology of the prenatal PolyI:C model with particular emphasis on its implementation in the mouse species. I shall highlight that the mouse PolyI:C model can successfully examine the influence of the precise timing of maternal immune activation, the role of pro- and anti-inflammatory cytokines, and the contribution of gene-environment interactions in the association between prenatal immune challenge and postnatal brain dysfunctions relevant to schizophrenia. Finally, I shall review how the PolyI:C model offers a unique opportunity to study the ontogeny of abnormal brain and behavioral functions and establish and evaluate early preventive interventions aiming to reduce the risk of long-lasting brain dysfunctions following prenatal exposure to infection.
