Impact of thyroid hormone deficiency on the developing CNS: cerebellar glial and neuronal protein expression in rat neonates exposed to antithyroid drug propylthiouracil.
Impact of thyroid hormone deficiency on the developing CNS: cerebellar glial and neuronal protein expression in rat neonates exposed to antithyroid drug propylthiouracil.
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甲状腺激素缺乏对中枢神经系统发育的影响：暴露于抗甲状腺药物丙硫氧嘧啶的大鼠新生儿的小脑胶质细胞和神经元蛋白表达。
DOI：
10.1080/14734220410029650
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Sajdel-Sulkowska,ElizabethM
中科院分区：
文献类型：
--
作者：
Li,Gui-Hua;Post,Jennifer;Koibuchi,Noriyuki;Sajdel-Sulkowska,ElizabethM
发育中的大鼠小脑易受甲状腺激素(TH)缺乏的影响。本研究探讨了参与这一反应的分子机制。具体地说，这项研究侧重于选定的小脑蛋白的表达，这些蛋白直接[表达3-岩藻糖基-N-乙酰乳糖胺抗原(CD15)，神经细胞黏附分子(L1)的蛋白]或间接[胶质纤维酸性蛋白(GFAP)]，参与神经胶质细胞与神经元的相互作用，从而调节细胞增殖和颗粒细胞迁移。比较了胎龄16天至出生后21天接受抗甲状腺药物丙基硫氧嘧啶(PTU)治疗的新生大鼠的小脑质量、结构和蛋白表达，并与从出生第1天开始接受甲状腺激素(T4)替代治疗的大鼠或未经治疗的对照组进行了比较。用定量免疫印迹法检测小脑蛋白质含量。PTU处理的大鼠生长迟缓，在第15天表现出小脑质量减少和小脑结构改变。T4新生儿的日常治疗恢复了正常的小脑/体质量比、小脑结构和小脑蛋白表达。免疫印迹密度分析显示，甲状腺功能减退症新生儿的小脑中特定蛋白的表达发生了变化。P10时CD15表达减少(46%，p=0.031)，并伴有胶质纤维酸性蛋白表达降低(%，p=0.039)。此外，在PTU治疗的小脑中观察到发育中的GFAP图谱的变化。在甲状腺功能低下的小脑中，L1的表达没有受到明显影响。小脑蛋白表达的改变可能会影响细胞间的相互作用，从而影响细胞的增殖和迁移，并有助于甲状腺功能低下大鼠新生儿的结构和功能改变。
The developing rat cerebellum is vulnerable to thyroid hormone (TH) deficiency. The present study addresses the molecular mechanisms involved in this response. Specifically, the study focuses on the expression of selected cerebellar proteins that are known to be directly [protein expressing 3-fucosyl-N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (L1)] or indirectly [glial fibrillary acidic protein (GFAP)], involved in glial-neuronal interactions and thus regulation of cell proliferation and granule cell migration. Cerebellar mass, structure, and protein expression in rat neonates exposed to antithyroid drug propylthiouracil (PTU) from the embryonic day (E) 16 to postnatal day (P) 21 were compared against rat neonates that received replacement of thyroxin (T4) starting on day P1 or untreated controls. Cerebellar proteins were analyzed by quantitative Western blots. PTU-treated rats lagged in growth and showed reduction in cerebellar mass and alterations in cerebellar structure on P15. Daily treatment of neonates with T4 restored normal cerebellum-to-body-mass ratio, cerebellar structure, and cerebellar protein expression. Densitometric analysis of Western blots revealed altered expression of selected proteins in the cerebella of hypothyroid neonates. A decrease of CD15 (46%,p= 0.031) was observed on P10 and was accompanied by a decrease in GFAP expression (64%, p= 0.039). Furthermore, a shift in the developmental GFAP profile was observed in the PTU-treated cerebellum. L1 expression was not significantly affected in the hypothyroid cerebellum. Altered expression of cerebellar proteins is likely to affect cell-cell interactions and consequently cell proliferation and migration and contribute to structural and functional alterations seen in the hypothyroid rat neonates.