Department of Pathology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China.
Int J Biol Sci. 2013;9(2):209-18. doi: 10.7150/ijbs.5646. Epub 2013 Feb 12.
Congenital hypothyroidism (CH) can lead to irreversible central nervous system (CNS) damage. However, the pathogenesis of the developmental brain disorders caused by CH has not been completely elucidated. ARPC5 and CRMP2 are closely associated with neurite outgrowth in brain development. Thus, the aim of the present study was to determine whether CRMP2B and ARPC5 expression is altered in the developing cerebral cortex of rats with CH. Control rats and rats with hypothyroidism were sacrificed at birth and at 15 days postpartum. We performed qRT-PCR to detect differences in the crmp2B and arpc5 mRNA expression in the right half of the frontal cortex of these rats. Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression. Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5. Results showed increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism. These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B. CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization.
先天性甲状腺功能减退症 (CH) 可导致中枢神经系统 (CNS) 不可逆转的损伤。然而，CH 引起的发育性脑障碍的发病机制尚未完全阐明。ARPC5 和 CRMP2 与脑发育中的轴突生长密切相关。因此，本研究旨在确定 CH 大鼠发育中的大脑皮质中 CRMP2B 和 ARPC5 的表达是否发生改变。对照组大鼠和甲状腺功能减退症大鼠分别在出生时和产后 15 天处死。我们进行 qRT-PCR 以检测这些大鼠右半额皮质中 crmp2B 和 arpc5 mRNA 表达的差异。然后使用 Western blot 检测 CRMP2B 和 ARPC5 蛋白表达的差异。此外，我们对左半额皮质进行免疫组织化学分析，以检测 CRMP2B 和 ARPC5 的异常定位。结果表明，甲状腺功能减退症大鼠皮质神经元中 CRMP2B 的核短异构体表达增加，全长 CRMP2B 和 ARPC5 表达减少。这些发现表明，甲状腺激素水平降低可抑制全长 CRMP2B 和 ARPC5 的表达，并促进 CRMP2B 短异构体的核转化。CRMP2B 和 ARPC5 可能通过诱导轴突生长抑制和细胞骨架蛋白解聚参与甲状腺功能减退症介导的中枢神经系统损伤。
