Magnetic resonance imaging (MRI) data of children with late diagnosed congenital hypothyroidism and cognitive alterations such as abnormal verbal memory processing suggest altered telencephalic commissural connections. The corpus callosum (CC) is the major inter-hemispheric commissure that contra-laterally connects neocortical areas. However, in late diagnosed neonates with congenital hypothyroidism, the possible effect of early transient and chronic postnatal hypothyroidism still remains unknown. We have studied the development of the anterior, middle and posterior CC, using in vivo MRI and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group, as a model for early transient hypothyroidism, was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to 21. Another group modeling chronic hypothyroid, were treated with MMI from P0 to 150 and from embryonic day 10 to P170. The results obtained from these groups were compared with same age control rats. The normalized T2 signal obtained using MRI was higher in MMI-treated rats and correlated with a low number and percentage of myelinated axons. The number and density of myelinated axons decreased in transient and chronic hypothyroid rats at P150. The g-ratio (inner to outer diameter ratio) and the estimated conduction velocity of myelinated axons were similar between MMI-treated and controls, but the conduction delay decreased in the posterior CC of MMI-treated rats compared to controls. These data show that early postnatal transient and chronic hypothyroidism alters CC maturation in a way that may affect the callosal transfer of information. These alterations cannot be reversed after delayed T4-treatment. Our data support the findings of neurocognitive delay in late T4-treated children with congenital hypothyroidism.

中文翻译：

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哺乳期短暂性甲状腺功能减退症会改变大鼠胼胝体的发育。体内磁共振图像和电子显微镜研究。


晚期诊断出先天性甲状腺功能减退症和言语记忆处理异常等认知改变的儿童的磁共振成像（MRI）数据表明端脑连合连接发生了改变。胼胝体（CC）是主要的半球间连合，对侧连接新皮质区域。然而，对于晚期诊断的先天性甲状腺功能减退症新生儿，早期短暂性和慢性产后甲状腺功能减退症的可能影响仍不清楚。我们利用体内 MRI 和电子显微镜研究了甲状腺功能减退和对照雄性大鼠的前部、中部和后部 CC 的发育。研究了四组甲硫咪唑 (MMI) 治疗的大鼠。一组作为早期短暂性甲状腺功能减退症模型，从出生后 (P) 0 到 P21 接受 MMI 治疗；其中一些大鼠还从 P15 到 21 接受 L-甲状腺素 (T4) 治疗。另一组模拟慢性甲状腺功能减退症，从 P0 到 150 以及胚胎第 10 天到 P170 接受 MMI 治疗。将这些组获得的结果与同龄对照大鼠进行比较。使用 MRI 获得的标准化 T2 信号在 MMI 治疗的大鼠中较高，并且与有髓鞘轴突的数量和百分比较低相关。在 P150 时，暂时性和慢性甲状腺功能减退大鼠的有髓轴突数量和密度减少。 MMI 处理组和对照组之间的 g 比（内径与外径比）和估计的有髓轴突传导速度相似，但与对照组相比，MMI 处理组大鼠后部 CC 的传导延迟有所减少。这些数据表明，出生后早期的短暂性和慢性甲状腺功能减退症会以可能影响胼胝体信息传递的方式改变CC成熟。 延迟 T4 治疗后，这些改变无法逆转。我们的数据支持晚期 T4 治疗的先天性甲状腺功能减退症儿童神经认知延迟的发现。