Suo Guihai, Shen Feifei, Sun Baolan, Song Honghua, Xu Meiyu, Wu Youjia
Neuroreport. 2018 Aug 1;29(11):877-882. doi: 10.1097/WNR.0000000000001047.
EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.
EphA5与其配体ephrin - A5的相互作用可在海马体早期发育过程中触发突触形成。我们之前报道过，EphA5表达异常可导致先天性甲状腺功能减退症（CH）大鼠出现突触形成障碍。为了更好地理解其精确的分子机制，我们进一步分析了CH大鼠海马体中ephrin - A5的表达特征。我们的研究表明，甲状腺激素缺乏会使大鼠发育中的海马体和海马神经元中的ephrin - A5表达下调。对甲状腺功能减退的海马体进行甲状腺素治疗以及对甲状腺功能减退的海马神经元进行三碘甲状腺原氨酸治疗可显著改善ephrin - A5的表达，但无法将其表达恢复到对照水平。体外培养的甲状腺功能减退的海马神经元表现出突触形成障碍，其特征为神经突数量和长度减少。此外，NMDAR - 1（NR1）、PSD95和CaMKII等与突触形成相关的分子表达均相应下调。这些结果表明，CH中ephrin - A5的表达可能降低，且ephrin - A5/EphA5信号的异常激活会影响大脑发育过程中的突触形成。这些发现为从基因角度探索CH的发病机制提供了重要依据。
