Thyroid hormone action in the adult brain: Gene expression profiling of the effects of single and multiple doses of triiodo-L-thyronine in the rat striatum

被引:61
作者
Diez, Diego [1 ]
Grijota-Martinez, Carmen [1 ,2 ]
Agretti, Patrizia [3 ]
De Marco, Giuseppina [3 ]
Tonacchera, Massimo [3 ]
Pinchera, Aldo [3 ]
Morreale de Escobar, Gabriella [1 ,2 ]
Bernal, Juan [1 ,2 ]
Morte, Beatriz [1 ,2 ]
机构
[1] CSIC, Inst Invest Biomed, E-28029 Madrid, Spain
[2] Inst Salud Carlos III, CIBERER, Madrid 28029, Spain
[3] Univ Pisa, Ctr Eccellenza AmbiSEN, Dept Endocrinol & Metab, I-56124 Pisa, Italy
关键词
D O I
10.1210/en.2008-0350
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thyroid hormones have profound effects on mood and behavior, but the molecular basis of thyroid hormone action in the adult brain is relatively unknown. In particular, few thyroid hormone-dependent genes have been identified in the adult brain despite extensive work carried out on the developing brain. In this work we performed global analysis of gene expression in the adult rat striatum in search for genomic changes taking place after administration of T-3 to hypothyroid rats. The hormone was administered in two different schedules: 1) a single, large dose of 25 mu g per 100 g body weight (SD) or 2) 1.5 mu g per 100 g body weight once daily for 5 d (RD). Twenty-four hours after the single or last of multiple doses, gene expression in the striatum was analyzed using Codelink microarrays. SD caused up-regulation of 149 genes and down-regulation of 88 genes. RD caused up-regulation of 18 genes and down-regulation of one gene. The results were confirmed by hybridization to Affymetrix microarrays and by TaqMan PCR. Among the genes identified are genes involved in circadian regulation and the regulation of signaling pathways in the striatum. These results suggest that thyroid hormone is involved in regulation of striatal physiology at multiple control points. In addition, they may explain the beneficial effects of large doses of thyroid hormone in bipolar disorders.
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收藏
页码:3989 / 4000
页数:12
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