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分析 EphA5 受体在发育中大鼠脑内的表达:先天性甲状腺功能减退症模型的体内研究。

Analysis of EphA5 receptor in the developing rat brain: an in vivo study in congenital hypothyroidism model.

机构信息

Department of Pediatric Healthcare, Children's Hospital of Soochow University, 303 Jingde Road, Suzhou 215003, Jiangsu Province, China.

出版信息

Eur J Pediatr. 2013 Aug;172(8):1077-83. doi: 10.1007/s00431-013-2008-5. Epub 2013 May 1.

Abstract

UNLABELLED

The EphA5 receptor has recently been known to play an important role in the initiation of the early phase of synaptogenesis, during which irreparable harm would be done to the developing brain in the absence of sufficient thyroid hormone (TH). In the present article, we aimed to analyze the characteristics of EphA5 receptor expression in the brain of congenital hypothyroid rats. The results showed that the levels of the EphA5 receptor were downregulated by TH deficiency in the developing rat brain with remarkable spatial and temporal characteristics. In the hypothyroid rats, the mRNA and protein levels of EphA5 receptor decreased significantly in the hippocampus (27.92-53.26%), cerebral cortex (12.52-47.16%), and cerebellum (8.72-31.69%) compared with those in the normal rats from postnatal day 0 (P0) to P21 (p < 0.01). The expression of EphA5 receptor was highest and declined most as much as 53% in the hippocampus with TH deficiency. At P7, the EphA5 receptor decreased most prominently during all the observed time point.

CONCLUSION

The EphA5 receptor plays actively in the brain development in congenital hypothyroid rats. Our study highlights the high expression of EphA5 receptor protein in hippocampus and dramatic changes at P7 in condition of TH deficiency, which may provide important basis for further investigations in manipulating congenital hypothyroidism.

摘要

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EphA5 受体最近被发现在突触发生的早期阶段(如果甲状腺激素(TH)不足,这一阶段会对发育中的大脑造成不可挽回的损害)中发挥重要作用。在本文中,我们旨在分析先天性甲状腺功能减退大鼠脑内 EphA5 受体表达的特征。结果表明,TH 缺乏下调了发育中大鼠脑内 EphA5 受体的水平,具有显著的时空特征。在甲状腺功能减退大鼠中,与正常大鼠相比,EphA5 受体的 mRNA 和蛋白水平在海马体(27.92-53.26%)、大脑皮层(12.52-47.16%)和小脑(8.72-31.69%)中均显著降低(p<0.01)。EphA5 受体在缺乏 TH 的情况下表达最高,下降最多可达 53%。在 P7 时,EphA5 受体在所有观察到的时间点下降最为明显。

结论

EphA5 受体在先天性甲状腺功能减退大鼠的大脑发育中发挥积极作用。我们的研究强调了 EphA5 受体蛋白在海马体中的高表达和 TH 缺乏时 P7 时的剧烈变化,这可能为进一步研究操纵先天性甲状腺功能减退症提供重要依据。

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