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DOI | 10.1210/en.2015-1643 |
Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats | |
Gilbert, M. E.1; Sanchez-Huerta, K.2; Wood, C.1 | |
发表日期 | 2016-02-01 |
ISSN | 0013-7227 |
卷号 | 157期号:2页码:774-787 |
英文摘要 | Severe thyroid hormone (TH) deficiency during critical phases of brain development results in irreversible neurological and cognitive impairments. The mechanisms accounting for this are likely multifactorial, and are not fully understood. Here we pursue the possibility that one important element is that TH affects basal and activity-dependent neurotrophin expression in brain regions important for neural processing. Graded exposure to propylthiouracil (PTU) during development produced dose-dependent reductions in mRNA expression of nerve growth factor (Ngf) in whole hippocampus of neonates. These changes in basal expression persisted to adulthood despite the return to euthyroid conditions in blood. In contrast to small PTU-induced reductions in basal expression of several genes, developmental PTU treatment dramatically reduced the activity-dependent expression of neurotrophins and related genes (Bdnf(t), Bdnf(iv), Arc, and Klf9) in adulthood and was accompanied by deficits in hippocampal-based learning. These data demonstrate that mild TH insufficiency during development not only reduces expression of important neurotrophins that persists into adulthood but also severely restricts the activity-dependent induction of these genes. Considering the importance of these neurotrophins for sculpting the structural and functional synaptic architecture in the developing and the mature brain, it is likely that TH-mediated deficits in these plasticity mechanisms contribute to the cognitive deficiencies that accompany developmental TH compromise. |
语种 | 英语 |
WOS记录号 | WOS:000369965900031 |
来源期刊 | ENDOCRINOLOGY |
来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/57232 |
作者单位 | 1.US EPA, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27709 USA; 2.Inst Politecn Nacl, Dept Fisiol Mauricio Russek, Escuela Nacl Ciencias Biol, Mexico City 07738, DF, Mexico |
推荐引用方式 GB/T 7714 | Gilbert, M. E.,Sanchez-Huerta, K.,Wood, C.. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats[J]. 美国环保署,2016,157(2):774-787. |
APA | Gilbert, M. E.,Sanchez-Huerta, K.,&Wood, C..(2016).Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats.ENDOCRINOLOGY,157(2),774-787. |
MLA | Gilbert, M. E.,et al."Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats".ENDOCRINOLOGY 157.2(2016):774-787. |
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