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Excess Thyroid Hormone Inhibits Embryonic Neural Stem/Progenitor Cells Proliferation and Maintenance through STAT3 Signalling Pathway

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Abstract

Hyperthyroidism is prevalent during pregnancy, but little is known about the effects of excess thyroid hormone on the development of embryonic neural stem/progenitor cells (NSCs), and the mechanisms underlying these effects. Previous studies indicate that STAT3 plays a crucial role in determining NSC fate during neurodevelopment. In this study, we investigated the effects of a supraphysiological dose of 3,5,3′-l-triiodothyronine (T3) on the proliferation and maintenance of NSCs derived from embryonic day 13.5 mouse neocortex, and the involvement of STAT3 in this process. Our results suggest that excess T3 treatment inhibits NSC proliferation and maintenance. T3 decreased tyrosine phosphorylation of JAK1, JAK2 and STAT3, and subsequently inhibited STAT3–DNA binding activity. Furthermore, proliferation and maintenance of NSCs were decreased by inhibitors of JAKs and STAT3, indicating that the STAT3 signalling pathway is involved in the process of NSC proliferation and maintenance. Taken together, these results suggest that the STAT3 signalling pathway is involved in the process of T3-induced inhibition of embryonic NSC proliferation and maintenance. These findings provide data for understanding the effects of hyperthyroidism during pregnancy on fetal brain development, and the mechanisms underlying these effects.

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Acknowledgments

We thank doctors Xubu Wang, Yutong Hao and Min Li for their hospitable and professional technical assistance. This work was supported by National Natural Science Foundation of China (Grant number: 30670490) and State Key Laboratory of Precision Spectroscopy.

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Authors and Affiliations

  1. Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China

    Chunhai Chen, Zhou Zhou, Min Zhong, Maoquan Li, Xuesen Yang, Yanwen Zhang, Yuan Wang, Aimin Wei, Mingyue Qu, Lei Zhang, Shangcheng Xu & Zhengping Yu

  2. State Key Laboratory of Precision Spectroscopy, Department of Physics, East China Normal University, Shanghai, China

    Shude Chen

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  1. Chunhai Chen
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  2. Zhou Zhou
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  13. Zhengping Yu
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Correspondence to Zhengping Yu.

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C. Chen and Z. Zhou contributed equally to this work.

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Chen, C., Zhou, Z., Zhong, M. et al. Excess Thyroid Hormone Inhibits Embryonic Neural Stem/Progenitor Cells Proliferation and Maintenance through STAT3 Signalling Pathway. Neurotox Res 20, 15–25 (2011). https://doi.org/10.1007/s12640-010-9214-y

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  • DOI: https://doi.org/10.1007/s12640-010-9214-y

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