Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 Rue Cuvier, 75005 Paris, France.
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, 1105 Amsterdam, the Netherlands.
Stem Cell Reports. 2022 Mar 8;17(3):459-474. doi: 10.1016/j.stemcr.2022.01.002. Epub 2022 Feb 3.
Neural stem cells (NSCs) in the adult brain are a source of neural cells for brain injury repair. We investigated whether their capacity to generate new neurons and glia is determined by thyroid hormone (TH) during development because serum levels peak during postnatal reorganization of the main NSC niche, the subventricular zone (SVZ). Re-analysis of mouse transcriptome data revealed increased expression of TH transporters and deiodinases in postnatal SVZ NSCs, promoting local TH action, concomitant with a burst in neurogenesis. Inducing developmental hypothyroidism reduced NSC proliferation, disrupted expression of genes implicated in NSC determination and TH signaling, and altered the neuron/glia output in newborns. Three-month-old adult mice recovering from developmental hypothyroidism had fewer olfactory interneurons and underperformed on short-memory odor tests, dependent on SVZ neurogenesis. Our data provide readouts permitting comparison with adverse long-term events following thyroid disruptor exposure and ideas regarding the etiology of prevalent neurodegenerative diseases in industrialized countries.
成体脑中的神经干细胞（NSCs）是脑损伤修复中神经细胞的来源。我们研究了它们生成新神经元和神经胶质细胞的能力是否由发育过程中的甲状腺激素（TH）决定，因为血清水平在主要 NSC 生态位（脑室下区，SVZ）的出生后重组期间达到峰值。对小鼠转录组数据的重新分析显示，出生后 SVZ NSCs 中 TH 转运体和脱碘酶的表达增加，促进了局部 TH 作用，伴随着神经发生的爆发。诱导发育性甲状腺功能减退症会减少 NSC 增殖，破坏与 NSC 决定和 TH 信号相关的基因的表达，并改变新生儿的神经元/神经胶质细胞输出。从发育性甲状腺功能减退症中恢复的 3 个月大的成年小鼠的嗅觉中间神经元较少，并且在依赖于 SVZ 神经发生的短期记忆气味测试中表现不佳。我们的数据提供了可与甲状腺破坏剂暴露后的不良长期事件进行比较的指标，并为工业化国家普遍存在的神经退行性疾病的病因提供了思路。
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