Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Reprod Toxicol. 2012 Aug;34(1):93-100. doi: 10.1016/j.reprotox.2012.03.005. Epub 2012 Apr 6.
To elucidate target molecules of white matter development responding to hypothyroidism, global gene expression profiling of cerebral white matter from male rat offspring was performed after maternal exposure to anti-thyroid agents, 6-propyl-2-thiouracil and methimazole, on postnatal day 20. Genes involved in central nervous system development commonly up- or down-regulated among groups treated with anti-thyroid agents. Immunohistochemical distributions of vimentin, Ret proto-oncogene (Ret), deleted in colorectal cancer protein (DCC), and Claudin11 (Cld11) were examined based on the gene expression profile. Immunoreactive cells for vimentin and Ret in the cingulum, and the immunoreactive intensity of Cld11 and DCC in whole white matter were increased by treatment with anti-thyroid agents. Immunoreactive cells for vimentin and Ret were immature astrocytes and oligodendrocytes, respectively. Thus, immunoreactive cells for vimentin and Ret may be quantitatively measurable targets of developmental hypothyroidism in white matter.
为了阐明甲状腺功能减退症作用的脑白质靶分子,在新生后第 20 天,对甲状腺药物(6-丙基-2-硫氧嘧啶和甲巯咪唑)处理的雄性仔鼠脑白质进行了全基因组表达谱分析。各组中与中枢神经系统发育相关的基因表现出普遍的上调或下调。根据基因表达谱,对波形蛋白、Ret 原癌基因(Ret)、结直肠癌缺失蛋白(DCC)和 Claudin11(Cld11)进行了免疫组织化学分布分析。抗甲状腺药物处理后,扣带回中的波形蛋白和 Ret 免疫反应性细胞以及全白质中 Cld11 和 DCC 的免疫反应性强度增加。波形蛋白和 Ret 的免疫反应性细胞分别为未成熟的星形胶质细胞和少突胶质细胞。因此,波形蛋白和 Ret 的免疫反应性细胞可能是脑白质发育性甲状腺功能减退症的定量可测量靶标。