Figueiredo B C, Otten U, Strauss S, Volk B, Maysinger D
Department of Pharmacology and Therapeutics, McGill University, Montreal, Que., Canada.
Brain Res Dev Brain Res. 1993 Apr 16;72(2):237-44. doi: 10.1016/0165-3806(93)90188-g.
Deficits or excesses of thyroid hormones during critical periods of mammalian cerebellar development can lead to profound biochemical and morphological abnormalities in this system. The goal of this study was to investigate the effects of perinatal hypo- and hyperthyroidism on the ontogeny of nerve growth factor (NGF) and its low-affinity receptor (p75NGFR) in the rat cerebellum. The concentration of NGF and of p75NGFR immunoreactivity (IR) were measured, several days after birth, in cerebella of rats which had received propylthiouracil (PTU) or thyroxine. NGF concentration was markedly enhanced only on postnatal day 2 (P2) in hyperthyroid rats, whereas in hypothyroid (PTU-treated) rats NGF values were similar to age-matched controls. These observations suggest that thyroid hormone affects NGF synthesis during early periods of cerebellar development. In Purkinje cells of control animals, p75NGFR IR peaked at P10. In hypothyroid rats, the expression of p75NGFR was retarded, peaking at P15, whereas in hyperthyroid rats it was advanced, peaking at P8. The increased p75NGFR IR found in Purkinje cell bodies and the delayed disappearance of p75NGFR IR from the external granular layer of hypothyroid rats suggest different roles for thyroid hormone in the developing cerebellum. We conclude that p75NGFR and NGF are independently regulated by thyroid hormone during critical periods of cerebellar development. The effect of thyroid hormone deficiency on p75NGFR content in Purkinje cells may involve complex mechanisms such as impaired efficiency of axonal transport.
在哺乳动物小脑发育的关键时期，甲状腺激素的缺乏或过量会导致该系统出现严重的生化和形态异常。本研究的目的是探讨围产期甲状腺功能减退和亢进对大鼠小脑神经生长因子（NGF）及其低亲和力受体（p75NGFR）个体发生的影响。在出生几天后，测量接受丙硫氧嘧啶（PTU）或甲状腺素的大鼠小脑内NGF浓度和p75NGFR免疫反应性（IR）。甲状腺功能亢进的大鼠仅在出生后第2天（P2）时NGF浓度显著升高，而甲状腺功能减退（PTU处理）的大鼠NGF值与年龄匹配的对照组相似。这些观察结果表明，甲状腺激素在小脑发育早期影响NGF的合成。在对照动物的浦肯野细胞中，p75NGFR IR在P10时达到峰值。在甲状腺功能减退的大鼠中，p75NGFR的表达延迟，在P15时达到峰值，而在甲状腺功能亢进的大鼠中则提前，在P8时达到峰值。在甲状腺功能减退大鼠的浦肯野细胞体中发现p75NGFR IR增加，且其从外颗粒层延迟消失，这表明甲状腺激素在发育中的小脑中具有不同作用。我们得出结论，在小脑发育的关键时期，p75NGFR和NGF由甲状腺激素独立调节。甲状腺激素缺乏对浦肯野细胞中p75NGFR含量的影响可能涉及复杂机制，如轴突运输效率受损。
