甲状腺激素与生长激素协调海马神经元生长发育的机制

项目名称： 甲状腺激素与生长激素协调海马神经元生长发育的机制

项目编号： No.30870924

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 万瑜

作者单位： 武汉大学

项目金额： 31万元

中文摘要： 婴幼儿先天性缺乏甲状腺激素（TH）将导致呆小症，而缺乏生长激素（GH）则导致矮小症(侏儒)。故传统上认为TH对脑的发育至关重要，而GH仅仅是一种躯体生长刺激素。本项目采用先天性甲状腺功能减退（CHT）的大鼠模型，发现甲低时海马锥体/颗粒层神经元减少、Nissl染色减弱；2、海马组织中GH/GHR/ JAK2/STAT5轴全面下调，该动物学习记忆能力显著下降。同时离体实验观察到：1）在培养的海马神经元、胶质细胞均有GHR表达；2）在TH的作用下，海马神经细胞中GH和GHR及其信号分子磷酸化（JAK2和STAT5）均显著增加；3）在5nM TH和10ng/mlGH的作用下，海马NSC分化成神经元显著高于TH或GH的单一效应，这些效应均可被GHR单克隆抗体部分抑制。本研究结果初次证明：TH能显著上调海马神经细胞中GH-GHR；GH-GHR同时介导了TH促中枢神经细胞生长发育的效应。这为重新认识GH和TH对中枢的生理作用，完善呆小症的发病机制，利用TH的允许作用优化GH的临床疗效提供了实验依据。

中文关键词： 生长激素；甲状腺激素；呆小症；海马；允许作用

英文摘要： The cretinism is usually caused by congenital hypothyroidism, and the dwarf, by growth hormone (GH) deficiency. For this reason, thyroid hormone (TH) is traditionall thought to be a more important hormone contributing to brain development than GH. However, recent researches have showed that GH is locally produced in the central nervous system (CNS), and can promote the proliferation and differentiation of embryo cerebral cortex neurons. According to the findings of our group and others, we hypothesize that, the fact that a peripherally GH deficiency does not lead to developmental disorder of intelligence is due to a local compensation of GH secreted in CNS; and as in periphery, TH may have a permissive action on the local GH in CNS. Due to hippocampal tissue is rich in receptors of both GH and TH, the present reseach plans to investigate the function of TH in regulation of GH secretion in fresh hippocampus slice and cultured hippocampal neural stem cells, and the effects of GH and TH, alone or incombination, on the structure and functions of the hippocampus in the rats with thyroid hypofunction or the dwarf rats with CNS GH receptor block.. This project may make a deeper insight into the cross-talk between GH and TH in CNS, providing novel information for etiology and therapy of cretinism.

英文关键词： Growth hormone; Thyroid hormone; Cretinism；Hippocampal; Permission