A transient placental source of serotonin for the fetal forebrain

Article

关键词: NORMAL ANXIETY-LIKE;    TRYPTOPHAN 2,3-DIOXYGENASE;    AGGRESSIVE-BEHAVIOR;    MONOAMINE-OXIDASE;    BRAIN-SEROTONIN;    EXPRESSION;    MICE;    TRANSPORTER;    NEURONS;    PREGNANCY;   

DOI  :  10.1038/nature09972

来源: SCIE

【 摘 要 】

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(1,2) 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-HT3. 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.

【 授权许可】

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