Patel A J, Smith R M, Kingsbury A E, Hunt A, Balázs R
Brain Res. 1980 Oct 6;198(2):389-402. doi: 10.1016/0006-8993(80)90752-0.
A study was made of the effects of age, neonatal hypothyroidism and hyperthyroidism on the development in rat brain of muscarinic cholinergic and GABA receptors. The former receptors were estimated by the binding of [3H]quinuclidinylbenzilate and the latter by binding of [3H]muscimol to crude membrane preparations from the forebrain and the cerebellum. In the normal forebrain, the density of muscarinic cholinergic receptors (in terms of unit membrane proteins) doubled during the period 6-35 days after birth. Thyroid state had relatively little effect on this development. In contrast, in the normal cerebellum the peak of the density of the receptors was attained in the early neonatal period followed by a progressive decline reaching about half of the maximum at day 35. Furthermore, in the cerebellum this development was significantly influenced by thyroid disorders: the rate of decrease in receptor density was accelerated by hyperthyroidism and retarded in thyroid deficiency. In comparison with euthyroid rats, the density of muscarinic receptors in the cerebellum was 30% lower in the hyperthyroidism (at day 21) and 40% higher in thyroid deficiency (at day 35). The increase in the density of GABA receptors with age was very small in the normal forebrain relative to the marked rise in the cerebellum. In the forebrain, thyroid state had no significant effect on this development. In contrast, in the cerebellum the ontogenesis of GABA receptors was advanced by thyroid hormone treatment and retarded in thyroid deficiency. However, by day 35 receptor density was normal in both conditions. Thyroid state had no significant influence on the affinity of either [3H]muscimol or the [3H]quinuclidinylbenzilate binding. The results suggest that thyroid hormone disorders during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems.
研究了年龄、新生儿甲状腺功能减退和甲状腺功能亢进对大鼠脑内毒蕈碱型胆碱能受体和GABA受体发育的影响。前者的受体通过[3H]喹核醇基苯甲酸酯的结合来评估，后者的受体通过[3H]蝇蕈醇与来自前脑和小脑的粗制膜制剂的结合来评估。在正常前脑中，毒蕈碱型胆碱能受体的密度（以单位膜蛋白计）在出生后6 - 35天期间增加了一倍。甲状腺状态对这一发育过程影响相对较小。相比之下，在正常小脑中，受体密度在新生儿早期达到峰值，随后逐渐下降，在第35天时降至最大值的约一半。此外，在小脑中，这一发育过程受到甲状腺疾病的显著影响：甲状腺功能亢进会加速受体密度的下降速率，而甲状腺功能减退则会使其减缓。与甲状腺功能正常的大鼠相比，甲状腺功能亢进的大鼠（在第21天）小脑中毒蕈碱受体的密度低30%，甲状腺功能减退的大鼠（在第35天）则高40%。在正常前脑中，GABA受体密度随年龄的增加非常小，相对于小脑的显著升高而言。在前脑中，甲状腺状态对这一发育过程没有显著影响。相比之下，在小脑中，甲状腺激素处理会促进GABA受体的个体发生，而甲状腺功能减退则会使其延迟。然而，到第35天时，两种情况下的受体密度均正常。甲状腺状态对[3H]蝇蕈醇或[3H]喹核醇基苯甲酸酯结合的亲和力没有显著影响。结果表明，生命早期的甲状腺激素紊乱可能导致几个中枢递质系统相对发育的扭曲，而不是同步变化。
