| First Author | Wu WL | Year | 2017 |
| Journal | Brain Behav Immun | Volume | 62 |
| Pages | 11-23 | PubMed ID | 27838335 |
| Mgi Jnum | J:319623 | Mgi Id | MGI:6859500 |
| Doi | 10.1016/j.bbi.2016.11.007 | Citation | Wu WL, et al. (2017) The placental interleukin-6 signaling controls fetal brain development and behavior. Brain Behav Immun 62:11-23 |
| abstractText | 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-6Ralpha) in placental trophoblasts (Cyp19-Cre(+);Il6ra(fl/fl)), and tested offspring of Cyp19-Cre(+);Il6ra(fl/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(+);Il6ra(fl/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. |
