Role of thyroid hormones in the maturation and organisation of rat barrel cortex.

The influence of thyroid hormones on cortical development was analysed in rat somatosensory cortex. Maternal and foetal hypothyroidism was induced and maintained by methimazole treatment from embryonic day 13 onwards. 5-Bromo-2'-deoxyuridine (BrdU) labelling in hypothyroid rats showed that cell positioning during corticogenesis followed an inside-out pattern. The radial neurogenetic gradients were more diffuse at all ages with respect to normal rats due to the inappropriate location of many cells, including those of the subcortical white matter. Most (62%) of the cells in the subcortical white matter of hypothyroid rats were labelled at embryonic day 15. Nissl staining of the primary somatosensory cortex showed blurred cortical layer boundaries and an abnormal barrel cytoarchitecture. Cytochrome oxidase and peanut agglutinin staining showed that the tangential organisation of the posteromedial barrel subfield and its layer IV specificity was not lost in hypothyroid rats. However the temporal pattern of peanut agglutinin labelling was delayed 3-4 days with respect to normal rats. In hypothyroid rats, the total barrelfield tangential area was reduced by 27% with respect to normal. The total tangential barrel area, corresponding to peanut agglutinin-negative labelling, occupied 77% of the barrelfield area and only 66% in hypothyroid rats. This reduction was larger with cytochrome oxidase staining where the total barrel area occupied 69% of the barrelfield area in normal and 46% in hypothyroid rats. Our data stress the importance of maternal and foetal thyroid hormones during development, and demonstrate the irreversible effects that maternal and foetal hypothyroidism may have on the intrinsic organisation and maturation of the neocortex.