Accession Number : ADA624272


Title :   Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders


Descriptive Note : Annual rept. 1 Jul 2014-30 Jun 2015


Corporate Author : UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES


Personal Author(s) : Bonnin, Alexandre ; Goeden, Nick ; Lund, Brett ; Anderson, George


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a624272.pdf


Report Date : Jul 2015


Pagination or Media Count : 35


Abstract : Several important milestones were reached during the second year of this award. First, we were able to demonstrate that maternal inflammation during pregnancy, triggered by the viralmimic poly(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 serotonergic system (blunting of axonal growth) and neuronal progenitor cell proliferation in specific forebrain regions. Thus our results demonstrate a direct molecular link between placental tryptophan metabolism and fetal brain development. A manuscript reporting these findings was submitted to the Journal of Neuroscience and is currently under review. In the second year of this award, we also started to investigate the possibility of pharmacologically interfering with this molecular pathway in order to potentially protect the fetal brain from the effects of maternal inflammation.


Descriptors :   *MENTAL DISORDERS , *PLACENTA , BRAIN , CELLS(BIOLOGY) , CLINICAL MEDICINE , DEVELOPMENTAL BIOLOGY , EXPOSURE(PHYSIOLOGY) , FETUS , GENE EXPRESSION , GROWTH(PHYSIOLOGY) , IMMUNOCHEMISTRY , IN SITU ANALYSIS , INFLAMMATION , METABOLISM , MICE , NERVE CELLS , NEUROPHYSIOLOGY , PREGNANCY , SEROTONIN , STATISTICAL ANALYSIS , TRYPTOPHAN


Subject Categories : Psychology
      Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE