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甲状腺激素不足会改变甲状腺功能减退症小鼠大脑在出生后早期与精神障碍相关分子的表达。

Thyroid hormone insufficiency alters the expression of psychiatric disorder-related molecules in the hypothyroid mouse brain during the early postnatal period.

机构信息

Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University, Sendai, Japan.

Laboratory of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

出版信息

Sci Rep. 2021 Mar 24;11(1):6723. doi: 10.1038/s41598-021-86237-8.

DOI:10.1038/s41598-021-86237-8
PMID:33762687
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7990947/
Abstract

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. TH insufficiency showed a decrease in the expression of parvalbumin (PV) in the cortex and hippocampus of pups at postnatal day (PD) 14, while treatment with thyroxine from PD 0 to PD 14 ameliorated the PV loss. On the other hand, treatment with antithyroid agents in adulthood did not result in a decrease in the expression of PV in these areas. These results indicate the existence of a critical period of TH action during the early postnatal period. A decrease in MeCP2-positive neuronal nuclei was also observed in the cortical layers II-IV of the cerebral cortex. The brains were then stained with CUX1, a marker for cortical layers II-IV. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II-IV of the mice was lower than that of normal mice. These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development.

摘要

本研究旨在探讨甲状腺激素 (TH) 在小鼠发育过程中皮质和海马中的功能作用。结果表明,出生后第 14 天(PD)时,甲状腺激素不足会导致皮质和海马中 PV 表达减少,而从 PD 0 到 PD 14 给予甲状腺素治疗则可改善 PV 缺失。另一方面,在成年期给予抗甲状腺药物治疗并不会导致这些区域的 PV 表达减少。这些结果表明,TH 在出生后早期的作用存在一个关键时期。此外,在大脑皮质的 II-IV 层中也观察到 MeCP2 阳性神经元核的减少。然后用 CUX1(皮质层 II-IV 的标志物)对大脑进行染色。与正常小鼠相比,甲状腺功能减退小鼠的体感皮层中 CUX1 信号减少,且这些小鼠的皮质层 II-IV 的总厚度低于正常小鼠。这些结果表明,围产期甲状腺激素不足会强烈而广泛地影响神经元发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/7990947/ee84d7e21fac/41598_2021_86237_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/7990947/ee84d7e21fac/41598_2021_86237_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/7990947/dadb457289bf/41598_2021_86237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/7990947/dff31eaf36a1/41598_2021_86237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/7990947/827820c47346/41598_2021_86237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/7990947/d85b619f0134/41598_2021_86237_Fig4_HTML.jpg
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