The Effects of Thyroid Hormone Insufficiency During Development On Cortical Morphology And The Behavioural Manifestations

The central hypothesis of this work is that developmental thyroid insufficiency impacts the development of the rat cerebral cortex by altering cortical volume and the number of cortical neurons. In addition, as these neuroanatomical changes caused by milder forms of developmental hypothyroidism or hypothyroxinemia may have both immediate and long term consequences on certain aspects of behaviour, the investigation sought to determine if the alterations in morphology, including the change in relative cortical volume, and the change in the number of cortical neurons in the rat brain, led to behavioral manifestations. Hypothyroidism was induced by the administration of graded levels of the antithyroid agent propylthiouracil (PTU) to suppress thyroid hormone production.;The number of neurons was estimated, using unbiased sampling techniques, to determine whether the cellular composition of cortex was altered following developmental TH insufficiency. To determine if these cortical alterations led to changes in behaviour, a battery of behavioural tests were performed which included maternal retrieval (PND 4), maternal separation anxiety (PND 6), Barnes maze (PND 48 and PND 86), social interaction social approach (PND 48-50), and open field (PND 46).;Taken together, the results presented here support the hypothesis that developmental hypothyroidism and hypothyroxinemia induced by chemical thyroid hormone suppression (PTU) cause alterations in the morphology of the cerebral cortex by altering cortical volume and changing the number of cortical neurons in the rat brain. Furthermore these alterations ultimately lead to changes in certain aspects of behaviour. These results have important clinical relevance because several studies suggest that developmental disabilities ranging from mild dyslexia to severe mental retardation can be attributed to alterations in cortical morphology resulting from abnormal cortical development.