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

U. Meyer, P. J. Murray, A. Urwyler, Kay Yan Benjamin Yee, M. Schedlowski, J. Feldon

Research output: Journal article publicationJournal articleAcademic researchpeer-review

176 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)208-221
Number of pages14
JournalMolecular Psychiatry
Volume13
Issue number2
DOIs
Publication statusPublished - 1 Feb 2008
Externally publishedYes

Keywords

  • Cytokines
  • Infection
  • Interleukin-10
  • Neurodevelopment
  • Pregnancy
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

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