Remaud Sylvie, Demeneix Barbara
Muséum National d'Histoire Naturelle, CNRS UMR 7221, Laboratoire Physiologie moléculaire de l'adaptation, 7 rue Cuvier 75005 Paris, France.
Biol Aujourdhui. 2019;213(1-2):7-16. doi: 10.1051/jbio/2019007. Epub 2019 Jul 5.
Thyroid hormones (THs) are vital for vertebrate brain function throughout life, from early development to ageing. Epidemiological studies show an adequate supply of maternal TH during pregnancy to be necessary for normal brain development, and this from the first trimester of onwards. Maternal TH deficiency irreversibly affects fetal brain development, increasing the risk of offspring cognitive disorders and IQ loss. Mammalian and non-mammalian (zebrafish, xenopus, chicken) models are useful to dissect TH-dependent cellular and molecular mechanisms governing embryonic and fetal brain development: a complex process including cell proliferation, survival, determination, migration, differentiation and maturation of neural stem cells (NSCs). Notably, rodent models have strongly contributed to understand the key neurogenic roles of TH still at work in adult life. Neurogenesis continues in two main areas, the sub-ventricular zone lining the lateral ventricles (essential for olfaction) and the sub-granular zone in the dentate gyrus of the hippocampus (involved in memory, learning and mood control). In both niches, THs tightly regulate the balance between neurogenesis and oligodendrogenesis under physiological and pathological contexts. Understanding how THs modulate NSCs determination toward a neuronal or a glial fate throughout life is a crucial question in neural stem cell biology. Providing answers to this question can offer therapeutic strategies for brain repair, notably in neurodegenerative diseases, demyelinating diseases or stroke where new neurons and/or oligodendrocytes are required. The review focuses on TH regulation of NSC fate in mammals and humans both during development and in the adult.
甲状腺激素(THs)在脊椎动物从早期发育到衰老的整个生命过程中对大脑功能至关重要。流行病学研究表明,孕期母体甲状腺激素的充足供应对正常大脑发育是必要的,且从妊娠早期开始就有此需求。母体甲状腺激素缺乏会不可逆转地影响胎儿大脑发育,增加后代认知障碍和智商损失的风险。哺乳动物和非哺乳动物(斑马鱼、非洲爪蟾、鸡)模型有助于剖析调控胚胎和胎儿大脑发育的甲状腺激素依赖性细胞和分子机制:这是一个复杂的过程,包括神经干细胞(NSCs)的细胞增殖、存活、命运决定、迁移、分化和成熟。值得注意的是,啮齿动物模型对理解甲状腺激素在成年期仍发挥的关键神经发生作用有很大贡献。神经发生在两个主要区域持续进行,即侧脑室壁的脑室下区(对嗅觉至关重要)和海马齿状回的颗粒下区(参与记忆、学习和情绪控制)。在这两个微环境中,甲状腺激素在生理和病理情况下都严格调节神经发生和少突胶质细胞生成之间的平衡。了解甲状腺激素如何在整个生命过程中调节神经干细胞向神经元或神经胶质细胞命运的决定,是神经干细胞生物学中的一个关键问题。为这个问题提供答案可以为脑修复提供治疗策略,特别是在神经退行性疾病、脱髓鞘疾病或中风等需要新神经元和/或少突胶质细胞的情况下。本文综述聚焦于甲状腺激素在哺乳动物和人类发育及成年期对神经干细胞命运的调控。