Aperçu: G.M.
Des
études épidémiologiques montrent que l'activation immunitaire
maternelle (MIA) pendant la grossesse est un facteur de risque pour
l'autisme. Cependant,
les mécanismes de la MIA affectant le développement du cerveau et les
comportements chez les descendants restent mal décrits.
Les résultats de l'étude démontrent que l'activation de l'IL-6 dans le placenta est
nécessaire pour transmettre les signaux inflammatoires au cerveau fœtal
et les comportements et les neuropathologies affectant le trouble neuro-dévelopemental.
Brain Behav Immun. 2017 May;62:11-23. doi: 10.1016/j.bbi.2016.11.007. Epub 2016 Nov 9.
The placental interleukin-6 signaling controls fetal brain development and behavior
Wu WL1, Hsiao EY2, Yan Z3, Mazmanian SK4, Patterson PH5.
Author information
- 1
- Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: wlwu@caltech.edu
- 2
- Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA; Department of Integrative Biology & Physiology, University of California, Los Angeles, 610 Charles E. Young Drive, Los Angeles, CA 90095, USA. Electronic address: ehsiao@ucla.edu.
- 3
- Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: Zihao_Yan@hms.harvard.edu.
- 4
- Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.
- 5
- Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: php@caltech.edu.
Abstract
Epidemiological studies show that maternal immune activation (MIA) during pregnancy is a risk factor for autism.
However, mechanisms for how MIA affects brain development and behaviors
in offspring remain poorly described. To determine whether placental
interleukin-6 (IL-6) signaling is required for mediating MIA on the
offspring, we generated mice with restricted deletion of the receptor
for IL-6 (IL-6Rα) in placental trophoblasts (Cyp19-Cre+;Il6rafl/fl), and tested offspring of Cyp19-Cre+;Il6rafl/fl
mothers for immunological, pathological and behavioral abnormalities
following induction of MIA. We reveal that MIA results in acute
inflammatory responses in the fetal brain. Lack of IL-6 signaling in
trophoblasts effectively blocks MIA-induced inflammatory responses in
the placenta and the fetal brain. Furthermore, behavioral abnormalities
and cerebellar neuropathologies observed in MIA control offspring are
prevented in Cyp19-Cre+;Il6rafl/fl offspring. Our
results demonstrate that IL-6 activation in placenta is required for
relaying inflammatory signals to the fetal brain and impacting behaviors
and neuropathologies relevant to neurodevelopmental disease.
Copyright © 2016 Elsevier Inc. All rights reserved.
- PMID: 27838335
- DOI: 10.1016/j.bbi.2016.11.007
