Data_Sheet_3_Transient Hypothyroidism During Lactation Alters the Development of the Corpus Callosum in Rats. An in vivo Magnetic Resonance Image and Electron Microscopy Study.PDF

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.

针对晚期确诊先天性甲状腺功能减退症且存在言语记忆加工异常等认知改变的儿童所采集的磁共振成像（magnetic resonance imaging, MRI）数据提示，其端脑连合纤维连接存在异常。胼胝体（corpus callosum, CC）是对侧性连接大脑新皮质区域的主要半球间连合纤维束。然而，针对晚期确诊的先天性甲状腺功能减退症新生儿，早期一过性及慢性产后甲状腺功能减退的潜在影响仍未明确。本研究通过活体磁共振成像及电子显微镜技术，对甲状腺功能减退模型与对照组雄性大鼠的胼胝体前部、中部及后部发育情况进行了分析。本研究共设置四组经他巴唑（methimazole, MMI）处理的大鼠：其中一组作为早期一过性甲状腺功能减退模型，于产后第0天（P0）至第21天（P21）经他巴唑处理；部分该组大鼠还于P15至P21期间接受了左甲状腺素（L-thyroxine, T4）干预。另一组作为慢性甲状腺功能减退模型，于P0至P150以及胚胎第10天至P170期间接受他巴唑处理。将上述各组的实验结果与同年龄段对照组大鼠进行对比。经磁共振成像检测得到的标准化T2信号在他巴唑处理组大鼠中更高，且与有髓轴突的数量及占比偏低存在相关性。在P150时，一过性及慢性甲状腺功能减退模型大鼠的有髓轴突数量与密度均出现下降。g值（g-ratio, 轴突内径与外径之比）以及有髓轴突的预估传导速度在他巴唑处理组与对照组间无显著差异，但他巴唑处理组大鼠胼胝体后部的传导延迟相较于对照组有所降低。上述数据表明，产后早期一过性及慢性甲状腺功能减退会改变胼胝体的成熟进程，进而可能影响胼胝体的信息传递功能。此类改变在延迟给予左甲状腺素干预后无法逆转。本研究数据佐证了晚期接受左甲状腺素治疗的先天性甲状腺功能减退症儿童存在神经认知发育迟缓的相关研究结果。