三碘甲状腺原氨酸在小脑颗粒细胞中诱导产生的神经营养因子-3促进浦肯野细胞分化。
Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation.
作者信息
Lindholm D, Castrén E, Tsoulfas P, Kolbeck R, Berzaghi M da P, Leingärtner A, Heisenberg C P, Tessarollo L, Parada L F, Thoenen H
机构信息
Department of Neurochemistry, Max Planck Institute for Psychiatry, Martinsried Munich, Federal Republic of Germany.
出版信息
J Cell Biol. 1993 Jul;122(2):443-50. doi: 10.1083/jcb.122.2.443.
Abstract
Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinje cells do not express NT-3 mRNA but do express trkC, the putative neuronal receptor for NT-3. Addition of recombinant NT-3 to cerebellar cultures from embryonic rat brain induces hypertrophy and neurite sprouting of Purkinje cells, and upregulates the mRNA encoding the calcium-binding protein, calbindin-28 kD. The present study demonstrates a novel interaction between cerebellar granule neurons and developing Purkinje cells in which NT-3 induced by T3 in the granule cells promotes Purkinje cell differentiation.
摘要
甲状腺激素在大脑发育中起重要作用，但三碘甲状腺原氨酸（T3）介导神经元分化的机制仍知之甚少。在此，我们证明T3在细胞培养和体内均能调节发育中大鼠小脑颗粒细胞中的神经营养因子——神经营养素-3（NT-3）。原位杂交实验表明，发育中的浦肯野细胞不表达NT-3 mRNA，但表达trkC，即NT-3的假定神经元受体。将重组NT-3添加到来自胚胎大鼠脑的小脑培养物中，可诱导浦肯野细胞肥大和神经突萌发，并上调编码钙结合蛋白（钙结合蛋白-28 kD）的mRNA。本研究证明了小脑颗粒神经元与发育中的浦肯野细胞之间存在一种新的相互作用，其中颗粒细胞中由T3诱导的NT-3促进浦肯野细胞分化。
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