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Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

Molecular Psychiatry volume 13, pages 208–221 (2008)Cite this article

Abstract

Maternal infections during pregnancy increase the risk for schizophrenia and related disorders of putative neurodevelopmental origin in the offspring. This association has been attributed to enhanced expression of pro-inflammatory cytokines in the fetal environment in response to maternal immunological stimulation. In contrast, the specific roles of anti-inflammatory cytokines are virtually unknown in this context. Here, we demonstrate that genetically enforced expression of the anti-inflammatory cytokine interleukin (IL)-10 by macrophages attenuates the long-term behavioral and pharmacological consequences of prenatal immune activation in a mouse model of prenatal viral-like infection by polyriboinosinic–polyribocytidilic acid (PolyI:C; 2 mg/kg, intravenously). In the absence of a discrete prenatal inflammatory stimulus, however, enhanced levels of IL-10 at the maternal–fetal interface by itself also precipitates specific behavioral abnormalities in the grown offspring. This highlights that in addition to the disruptive effects of excess pro-inflammatory molecules, a shift toward enhanced anti-inflammatory signaling in prenatal life can similarly affect cognitive and behavioral development. Hence, shifts of the balance between pro- and anti-inflammatory cytokine classes may be a critical determinant of the final impact on neurodevelopment following early life infection or innate immune imbalances.

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Acknowledgements

The present study was supported by grants awarded by the Swiss Federal Institute of Technology (ETH). Joram Feldon and Benjamin K Yee received additional support from the National Centre for Competence in Research: Neural Plasticity & Repair, funded by the Swiss National Science Foundation. We are extremely grateful to Dr Irene Knuesel and Ms Liz Weber for breeding and genotyping the animals, to Peter Schmid for his excellent technical support, to Natalie Aeschbach-Jones for her editorial support, and to the Animal Services Department in Schwerzenbach for animal husbandry and care.

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  1. M Schedlowski

    Present address: 4Current address: Institute of Medical Psychology and Behavioral Immunobiology, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.,

Authors and Affiliations

  1. Laboratory of Behavioural Neurobiology, ETH Zurich, Schwerzenbach, Switzerland

    U Meyer, B K Yee & J Feldon

  2. Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA

    P J Murray

  3. Laboratory of Psychology and Behavioural Immunobiology, ETH Zurich, CAB, Zurich, Switzerland

    A Urwyler & M Schedlowski

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Correspondence to U Meyer or J Feldon.

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Meyer, U., Murray, P., Urwyler, A. et al. Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling. Mol Psychiatry 13, 208–221 (2008). https://doi.org/10.1038/sj.mp.4002042

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