Balázs R, Gallo V, Atterwill C K, Kingsbury A E, Jørgensen O S
Biomed Biochim Acta. 1985;44(10):1469-82.
The following hypotheses were tested: is the degeneration of differentiating granule cells in the internal granular layer of the thyroid deficient cerebellum due to a direct requirement of these cells for thyroid hormone, or is it mediated through the failure of some of these cells to make synaptic contact with the hypoplastic Purkinje cells? The effect of thyroid hormone (T3) was studied in rat cerebellar cultures which contain predominantly granule cells. The cultures were grown in a chemically defined medium (S-) in the presence or absence of T3, and were also compared with serum (and thus thyroid hormone) containing cultures (S+). It would appear that T3 is not essential for the relatively long-term survival of the granule cells. Furthermore, cell growth in terms of protein accretion, and the morphological appearance of the cultures were also similar in S- in the presence and absence of T3. Maturation of granule cells was followed by estimating indices, which in the cerebellum in vivo are influenced by the hormone. However, developmental changes affecting the D2 protein, which is implicated in adhesion among nerve cells, and muscarinic receptor binding were not influenced by T3 in vitro. The voltage (veratridine)-sensitive uptake of 22Na was also unaffected, although T3 increased the rate of the relatively small veratridine insensitive component of the 22Na-influx. However, in comparison with cells grown in S+, the rate of both the veratridine sensitive and insensitive component of 22Na-influx was similar under serum-free conditions, whereas the maturation of the D2 protein and muscarinic receptor binding was retarded. The failure of thyroid hormone to influence the differentiation of granule cells, is not due to the in vitro conditions, since T3 is known to have a marked effect on the maturation of certain other classes of neural cells in culture. The results are consistent with the view that the effect of thyroid hormone on neural maturation is cell-type specific, and that granule cells are not targets of thyroid hormone action. They support our second hypothesis, that is, that the degeneration of granule cells in thyroid deficiency is a consequence of the reduction in available postsynaptic sites for the granule cell axons due to the retarded differentiation of Purkinje cells.
甲状腺功能减退的小脑内颗粒层中正在分化的颗粒细胞的退化，是由于这些细胞对甲状腺激素的直接需求，还是通过这些细胞中的一些未能与发育不全的浦肯野细胞建立突触联系介导的？在主要含有颗粒细胞的大鼠小脑培养物中研究了甲状腺激素（T3）的作用。培养物在化学限定培养基（S-）中生长，存在或不存在T3，并与含血清（因此含有甲状腺激素）的培养物（S+）进行比较。似乎T3对于颗粒细胞的相对长期存活不是必需的。此外，在存在和不存在T3的情况下，S-中培养物的蛋白质积累方面的细胞生长以及形态外观也相似。通过估计指标来跟踪颗粒细胞的成熟，这些指标在体内小脑中受该激素影响。然而，影响神经细胞间黏附的D2蛋白以及毒蕈碱受体结合的发育变化在体外不受T3影响。尽管T3增加了22Na流入中相对较小的对藜芦碱不敏感成分的速率，但对22Na的电压（藜芦碱）敏感性摄取也未受影响。然而，与在S+中生长的细胞相比，在无血清条件下，22Na流入的藜芦碱敏感和不敏感成分的速率相似，而D2蛋白的成熟和毒蕈碱受体结合则受到抑制。甲状腺激素未能影响颗粒细胞的分化，并非由于体外条件，因为已知T3对培养中的某些其他类型神经细胞的成熟有显著影响。这些结果与以下观点一致，即甲状腺激素对神经成熟的影响是细胞类型特异性的，并且颗粒细胞不是甲状腺激素作用的靶标。它们支持了我们的第二个假设，即甲状腺功能减退时颗粒细胞的退化是由于浦肯野细胞分化延迟导致颗粒细胞轴突可用突触后位点减少的结果。
