Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders
Abstract
We demonstrated that maternal inflammation during pregnancy, triggered by the viral-mimicpoly(I:C), induces a significant increase of tryptophan metabolism in the placenta. This leads to a direct increased output of serotonin from the placenta to the fetal forebrain. Elevation of serotonin at these early stages of fetal brain development alters the development of the endogenous fetal serotonergic system (blunting of axonal growth) and neuronal progenitor cell proliferation in specific forebrain regions. We also demonstrated that pharmacologically interfering with this molecular pathway can potentially protect thefetal brain from the effects of maternal inflammation. Thus our results demonstrate a direct molecular link between maternal inflammation during pregnancy, placental tryptophan metabolism and fetal brain development. A manuscript reporting these findings was published in the Journal of Neuroscience.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1018473
Entities
People
- Alexandre Bonnin
- Brett T Lund
- George P. Anderson
- Nick Goeden
Organizations
- University of Southern California