title: Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling.
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.
authors.affiliation: Laboratory of Behavioural Neurobiology, ETH Zurich, Schwerzenbach, Switzerland. meyer@behav.biol.ethz.ch
authors.forename: U
authors.initials: U
authors.lastname: Meyer
authors.forename: P J
authors.initials: PJ
authors.lastname: Murray
authors.forename: A
authors.initials: A
authors.lastname: Urwyler
authors.forename: B K
authors.initials: BK
authors.lastname: Yee
authors.forename: M
authors.initials: M
authors.lastname: Schedlowski
authors.forename: J
authors.initials: J
authors.lastname: Feldon
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001245:Association Learning / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000254:growth & development / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007266:Inhibition, Psychological; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D011070:Poly I-C / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D011070:Poly I-C