Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders
Technical Report,01 Jul 2013,30 Jun 2016
University of Southern California Los Angeles United States
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We demonstrated that maternal inflammation during pregnancy, triggered by the viral-mimicpolyIC, 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.