A transient placental source of serotonin for the fetal forebrain |
| |
Authors: | Bonnin Alexandre Goeden Nick Chen Kevin Wilson Melissa L King Jennifer Shih Jean C Blakely Randy D Deneris Evan S Levitt Pat |
| |
Affiliation: | Zilkha Neurogenetic Institute, Keck School of Medicine of USC, Los Angeles, California 90089, USA. bonnin@usc.edu |
| |
Abstract: | Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1(-/-) (also called Fev) mice in which most dorsal raphe neurons lack 5-HT. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|