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.
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Meyer et al. suggested that maternal IL-10 may attenuate behavioral and pharmacological dysfunctions in a poly(I:C) MIA model.
“A poly(I:C) MIA model by Meyer et al (2008) suggested that maternal IL-10 may be able to attenuate behavioral and pharmacological dysfunctions.”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Meyer et al, 2008
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- Authors
- Meyer, U., Murray, P. J., Urwyler, A., Yee, B. K., Schedlowski, M., & Feldon, J.
- Affiliations
- ETH Zurich (CH)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Meyer, U
- Feldon, J
- Venue
- Molecular Psychiatry
- Published
- 2007-06-19
- Volume
- 13
- Issue
- 2
- Pages
- 208-221
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2034427457
- Cited by
- 252
- References
- 8
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 8 · 2023: 6 · 2022: 14 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 14 · 2017: 9 · 2016: 19 · 2015: 18 · 2014: 14 · 2013: 14 · 2012: 15
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- prenatal immune activation, IL-10, anti-inflammatory cytokines, inflammatory cytokines, maternal infection, schizophrenia, brain development, macrophages, poly(I:C), behavioral abnormalities, cognitive development, innate immunity, maternal-fetal interface
- MeSH terms
- Animals, Animals, Newborn, Association Learning, Behavior, Animal, Brain, Disease Models, Animal, Drug Interactions, Female, Gene Expression Regulation, Inhibition, Psychological, Macrophages, Male, Mice, Transgenic, Motor Activity, Poly I-C, Pregnancy, Prenatal Exposure Delayed Effects, Time Factors, Signal Transduction, Cytokines, Interleukin-10, Mice
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