Sawin S, Brodish P, Carter C S, Stanton M E, Lau C
Mantech Environmental Sciences, University of North Carolina, Chapel Hill, USA.
Neurotoxicol Teratol. 1998 Nov-Dec;20(6):627-35. doi: 10.1016/s0892-0362(98)00020-8.
The effects of hypothyroidism on development of cholinergic system in brain regions (prefrontal cortex and hippocampus) were evaluated by measuring choline acetyltransferase (ChAT) activity and hemicholinium-3 binding to the high-affinity choline transporter. Various degrees of thyroid deficiency were produced by perinatal exposure to propylthiouracil (PTU) in drinking water ranging from 5 ppm (mg/l) to 25 ppm beginning at gestational day 18 until postnatal day 21. ChAT, a marker for cholinergic nerve terminals, was reduced by PTU in a dose-dependent manner. Concomitant with the enzyme deficits, hemicholinium-3 binding was elevated, suggesting an increase in neuronal impulse activity. Although similar changes were seen in both brain regions examined, the magnitude and duration of these changes were more definitive in the prefrontal cortex. Nonetheless, these neurochemical alterations appeared to be recoverable when the rats returned to a euthyroid state, and no further changes were observed as the animals reached adulthood. In comparison, data reported in a succeeding article indicate that deficits in cognitive function were first seen in weanling hypothyroid rats, but that the behavioral impairments lasted well into adulthood when thyroid status and cholinergic parameters in the brain appeared to have recovered to normal. These results suggest that alterations of cholinergic system caused by perinatal hypothyroidism are associated with neurobehavioral deficits at weaning, and these developmental deviations may cause permanent impairment of cognitive function despite recovery from the hormonal imbalance at adult ages.
通过测量胆碱乙酰转移酶（ChAT）活性以及半胱氨酸-3与高亲和力胆碱转运体的结合情况，评估甲状腺功能减退对大脑区域（前额叶皮层和海马体）胆碱能系统发育的影响。从妊娠第18天开始至出生后第21天，通过在饮用水中添加5 ppm（mg/l）至25 ppm的丙硫氧嘧啶（PTU），造成不同程度的甲状腺功能减退。ChAT作为胆碱能神经末梢的标志物，其活性被PTU以剂量依赖的方式降低。与酶活性降低同时出现的是，半胱氨酸-3结合增加，提示神经元冲动活动增强。尽管在所检查的两个脑区都观察到了类似变化，但前额叶皮层这些变化的幅度和持续时间更为明显。然而，当大鼠恢复到甲状腺功能正常状态时，这些神经化学改变似乎是可恢复的，并且随着动物成年，未观察到进一步的变化。相比之下，后续一篇文章报道的数据表明，认知功能缺陷首先在断奶期甲状腺功能减退的大鼠中出现，但当大脑中的甲状腺状态和胆碱能参数似乎已恢复正常时，行为障碍仍持续到成年期。这些结果表明，围产期甲状腺功能减退引起的胆碱能系统改变与断奶期的神经行为缺陷有关，并且这些发育偏差可能导致认知功能的永久性损害，尽管在成年期激素失衡已恢复。
