Manzano Jimena, Bernal Juan, Morte Beatriz
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain.
Int J Dev Neurosci. 2007 May;25(3):171-9. doi: 10.1016/j.ijdevneu.2007.01.003. Epub 2007 Feb 13.
Thyroid hormone influences brain maturation through interaction with nuclear receptors and regulation of gene expression. Their role on astrocyte maturation remains unclear. We have analyzed the role of thyroid hormone in rat cerebellar astrocyte maturation by comparing the sequential patterns of intermediate filament expression in normal and hypothyroid animals. During normal development astroglial cells sequentially express nestin, vimentin, and glial fibrillary acidic protein. Differentiated astrocytes appeared in the superior medullary vellum by postnatal day 2 and reached the white mater and internal granular layer by postnatal day 4. Intermediate filament marker expression was transiently lost from postnatal days 6 to 8 in anterior lobes, without an increased apoptosis. Vimentin expression was replaced by glial fibrillary acidic protein between postnatal days 10 and 32. The differentiated astrocytes were evenly distributed throughout the cerebellar slices, including the internal granular layer. Differences between normal and hypothyroid rats were observed starting from postnatal day 4, with lack of differentiated astrocytes in the internal granular layer. The transient decrease of astrocyte markers immunoreactivity in the anterior lobe did not take place in hypothyroid rats. The vimentin-glial fibrillary acidic protein transition was delayed and most differentiated astrocytes remained confined to the white matter. The results indicate that thyroid hormone deficiency induces a delay and a partial arrest of astrocyte differentiation. Astrocytes express thyroid hormone receptor alpha and beta subtypes suggesting that astrocytes are direct target cells of thyroid hormones.
甲状腺激素通过与核受体相互作用和调节基因表达来影响大脑成熟。它们在星形胶质细胞成熟中的作用仍不清楚。我们通过比较正常和甲状腺功能减退动物中间丝表达的顺序模式，分析了甲状腺激素在大鼠小脑星形胶质细胞成熟中的作用。在正常发育过程中，星形胶质细胞依次表达巢蛋白、波形蛋白和胶质纤维酸性蛋白。出生后第2天，分化的星形胶质细胞出现在上髓帆，出生后第4天到达白质和内颗粒层。前叶在出生后第6至8天中间丝标记物表达短暂缺失，且凋亡未增加。波形蛋白表达在出生后第10天至32天被胶质纤维酸性蛋白取代。分化的星形胶质细胞均匀分布在整个小脑切片中，包括内颗粒层。从出生后第4天开始观察到正常大鼠和甲状腺功能减退大鼠之间的差异，内颗粒层缺乏分化的星形胶质细胞。甲状腺功能减退大鼠前叶星形胶质细胞标志物免疫反应性没有出现短暂下降。波形蛋白向胶质纤维酸性蛋白的转变延迟，大多数分化的星形胶质细胞仍局限于白质。结果表明，甲状腺激素缺乏会导致星形胶质细胞分化延迟和部分停滞。星形胶质细胞表达甲状腺激素受体α和β亚型，提示星形胶质细胞是甲状腺激素的直接靶细胞。
