Abstract
Prenatal exposure to infections represents a risk factor for the emergence of neuropsychiatric disorders in later life, including schizophrenia and autism. However, it remains essentially unknown whether this association is primarily attributable to prenatal and/or postnatal maternal effects on the offspring. Here, we addressed this issue by dissecting the relative contributions of prenatal inflammatory events and postnatal maternal factors in an animal model of prenatal viral-like infection. Pregnant mice were exposed to the inflammatory agent polyriboinosinic-polyribocytidilic acid (PolyI:C; 5 mg/kg, i.v.) or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were cross fostered to surrogate rearing mothers that had either experienced inflammatory or sham treatment during pregnancy. We demonstrate that a variety of dopamine- and glutamate-related pharmacological and neuroanatomical disturbances emerge after prenatal immune challenge regardless of whether neonates were raised by vehicle- or PolyI:C-exposed surrogate mothers. However, the adoption of prenatal control animals to immune-challenged surrogate mothers was also sufficient to induce specific pharmacological and neuroanatomical abnormalities in the fostered offspring. Multiple schizophrenia-related dysfunctions emerging after prenatal immune challenge are thus mediated by prenatal but not postnatal maternal effects on the offspring, but immunological stress during pregnancy may affect postpartum maternal factors in such a way that being reared by an immune-challenged surrogate mother can confer risk for distinct forms of psychopathology in adult life.
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Acknowledgements
The present study was supported by SNF Grant No. 3100AO-100309 and Grants of the Swiss Federal Institute of Technology No. TH-9/04-2 and TH-22/04-1. We are extremely grateful to Liz Weber, Peter Schmid, and Hannes Sigrist for their technical support, to Natalie Aeschbach-Jones for her editorial assistance, and to the Animal Services Department, Schwerzenbach for animal husbandry and care.
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Meyer, U., Nyffeler, M., Schwendener, S. et al. Relative Prenatal and Postnatal Maternal Contributions to Schizophrenia-Related Neurochemical Dysfunction after In Utero Immune Challenge. Neuropsychopharmacol 33, 441–456 (2008). https://doi.org/10.1038/sj.npp.1301413
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DOI: https://doi.org/10.1038/sj.npp.1301413
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