| Literature DB >> 27838335 |
Wei-Li Wu1, Elaine Y Hsiao2, Zihao Yan3, Sarkis K Mazmanian4, Paul H Patterson5.
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 <span class="Disease">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.Entities:
Keywords: Autism spectrum disorder (ASD); Hindbrain development; Interleukin-6 (IL-6); Maternal immune activation (MIA); Maternal-placental-fetal axis; Placenta; Purkinje cells
Mesh：
Substances：
Year: 2016 PMID： 27838335 PMCID： PMC5373986 DOI： 10.1016/j.bbi.2016.11.007
Source DB: PubMed Journal: Brain Behav Immun ISSN： 0889-1591 Impact factor: 7.217