A transient placental source of serotonin for the fetal forebrain.
A transient placental source of serotonin for the fetal forebrain.
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DOI：
10.1038/nature09972
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发表时间：
2011-04-21
期刊：
影响因子：
64.8
通讯作者：
Levitt, Pat
中科院分区：
文献类型：
--
作者：
Bonnin, Alexandre;Goeden, Nick;Chen, Kevin;Wilson, Melissa L.;King, Jennifer;Shih, Jean C.;Blakely, Randy D.;Deneris, Evan S.;Levitt, Pat
5-羟色胺（5-羟色胺；5-HT）被认为通过母胎相互作用调节神经发育过程，具有长期的心理健康影响。教条指出，除了胎儿的5-HT神经元，母体在怀孕期间对胎儿的5-HT也有显著的贡献，但这还没有经过实证检验。为了检验假定的胚胎脑5-HT的中枢和外周来源，我们使用了大多数中背（DR）神经元缺乏5-HT的Pet-1−/−小鼠。通过外源性5-羟色胺来源，5-羟色胺的测量揭示了胎儿早期和晚期前脑和后脑之间积累的先前未知的差异。我们证明这个来源不是母系的。利用额外的遗传策略、体外胎盘生物学研究的新技术和胎盘新合成的直接操作，我们研究了这一外源来源的性质，并在小鼠和人类中发现了母体色氨酸前体介导的胎盘5-HT合成途径。这项研究揭示了胎盘代谢途径在调节胎儿大脑发育中的一个新的直接作用，并暗示了新的母体-胎盘-胎儿相互作用，可能是5-羟色胺对长期心理健康结果显著影响的基础。
Serotonin (5-hydroxytryptamine; 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. Dogma states 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 the Pet-1−/− mice in which most dorsal raphe (DR) neurons lack 5-HT. Measures of 5-HT revealed previously unknown differences in accumulation between the fore- and hindbrain during early and late fetal stages, through an exogenous source of 5-HT. We show that this source 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 and 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 implicates novel maternal-placental-fetal interactions that could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.
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影响因子：
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