Préau Laetitia, Fini Jean Baptiste, Morvan-Dubois Ghislaine, Demeneix Barbara
UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
Biochim Biophys Acta. 2015 Feb;1849(2):112-21. doi: 10.1016/j.bbagrm.2014.06.015. Epub 2014 Jun 27.
The essential roles of thyroid hormone (TH) in perinatal brain development have been known for decades. More recently, many of the molecular mechanisms underlying the multiple effects of TH on proliferation, differentiation, migration, synaptogenesis and myelination in the developing nervous system have been elucidated. At the same time data from both epidemiological studies and animal models have revealed that the influence of thyroid signaling on development of the nervous system, extends to all periods of life, from early embryogenesis to neurogenesis in the adult brain. This review focuses on recent insights into the actions of TH during early neurogenesis. A key concept is that, in contrast to the previous ideas that only the unliganded receptor was implicated in these early phases, a critical role of the ligand, T3, is increasingly recognized. These findings are considered in the light of increasing knowledge of cell specific control of T3 availability as a function of deiodinase activity and transporter expression. These requirements for TH in the early stages of neurogenesis take on new relevance given the increasing epidemiological data on adverse effects of TH lack in early pregnancy on children's neurodevelopmental outcome. These ideas lead logically into a discussion on how the actions of TH during the first phases of neurogenesis can be potentially disrupted by gestational iodine lack and/or chemical pollution. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
几十年来，甲状腺激素（TH）在围产期脑发育中的重要作用已为人所知。最近，TH对发育中的神经系统的增殖、分化、迁移、突触形成和髓鞘形成产生多种影响的许多分子机制已被阐明。与此同时，流行病学研究和动物模型的数据都表明，甲状腺信号对神经系统发育的影响延伸至生命的各个时期，从早期胚胎发生到成体脑内的神经发生。本综述聚焦于对早期神经发生过程中TH作用的最新见解。一个关键概念是，与以往认为只有未结合配体的受体参与这些早期阶段的观点不同，配体T3的关键作用越来越受到认可。鉴于对作为脱碘酶活性和转运体表达函数的T3可利用性的细胞特异性控制的认识不断增加，这些发现得到了考虑。鉴于越来越多的流行病学数据表明，孕早期TH缺乏对儿童神经发育结局有不良影响，神经发生早期阶段对TH的这些需求具有了新的意义。这些观点顺理成章地引出了关于神经发生第一阶段TH的作用如何可能因孕期碘缺乏和/或化学污染而受到潜在干扰的讨论。本文是名为“动物发育中的核受体”的特刊的一部分。
