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甲状腺激素对成体神经干细胞命运的调控:啮齿类动物和灵长类动物的比较分析。

Thyroid hormone regulation of adult neural stem cell fate: A comparative analysis between rodents and primates.

机构信息

UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, Paris, France.

UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, Paris, France.

出版信息

Vitam Horm. 2021;116:133-192. doi: 10.1016/bs.vh.2021.02.009. Epub 2021 Mar 11.

Abstract

Thyroid hormone (TH) signaling, a highly conserved pathway across vertebrates, is crucial for brain development and function throughout life. In the adult mammalian brain, including that of humans, multipotent neural stem cells (NSCs) proliferate and generate neuronal and glial progenitors. The role of TH has been intensively investigated in the two main neurogenic niches of the adult mouse brain, the subventricular and the subgranular zone. A key finding is that T3, the biologically active form of THs, promotes NSC commitment toward a neuronal fate. In this review, we first discuss the roles of THs in the regulation of adult rodent neurogenesis, as well as how it relates to functional behavior, notably olfaction and cognition. Most research uncovering these roles of TH in adult neurogenesis was conducted in rodents, whose genetic background, brain structure and rate of neurogenesis are considerably different from that of humans. To bridge the phylogenetic gap, we also explore the similarities and divergences of TH-dependent adult neurogenesis in non-human primate models. Lastly, we examine how photoperiodic length changes TH homeostasis, and how that might affect adult neurogenesis in seasonal species to increase fitness. Several aspects by which TH acts on adult NSCs seem to be conserved among mammals, while we only start to uncover the molecular pathways, as well as how other in- and extrinsic factors are intertwined. A multispecies approach delivering more insights in the matter will pave the way for novel NSC-based therapies to combat neurological disorders.

摘要

甲状腺激素 (TH) 信号转导是一种高度保守的通路,存在于脊椎动物中,对大脑的发育和功能至关重要。在成年哺乳动物的大脑中,包括人类,多能神经干细胞 (NSC) 会增殖并产生神经元和神经胶质前体。TH 的作用在成年小鼠大脑的两个主要神经发生龛位(脑室下区和颗粒下区)中得到了深入研究。一个关键的发现是,TH 的生物活性形式 T3 促进 NSC 向神经元命运的分化。在这篇综述中,我们首先讨论了 TH 在调节成年啮齿动物神经发生中的作用,以及它如何与功能行为(特别是嗅觉和认知)相关。揭示 TH 在成年神经发生中的这些作用的大多数研究都是在啮齿动物中进行的,啮齿动物的遗传背景、大脑结构和神经发生速度与人类有很大的不同。为了弥合系统发育上的差距,我们还探讨了非人类灵长类动物模型中 TH 依赖性成年神经发生的相似性和差异性。最后,我们研究了光周期如何改变 TH 动态平衡,以及这如何影响季节性物种的成年神经发生以提高适应性。TH 作用于成年 NSC 的几个方面似乎在哺乳动物中是保守的,而我们才刚刚开始揭示分子途径,以及其他内在和外在因素是如何交织在一起的。多物种方法在这方面提供更多的见解,将为基于 NSC 的治疗方法治疗神经退行性疾病铺平道路。

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