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

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.