How Thyroid Hormones Shape the Brain

This chapter provides a comprehensive exploration of the role of thyroid hormones in the development of key brain structures: the cerebral cortex, hippocampus, striatum, and cerebellum, as well as the sense organs retina and cochlea. Hypothyroidism is generally associated with impairments in axodendritic development, synaptogenesis, neuron migration and differentiation, and myelination. In the developing cerebral cortex, hypothyroidism delays the appearance of Cajal-Retzius cells, critical for the proper migration of neurons, causing migration defects. The maturation of the transient subplate layer, crucial for establishing thalamocortical connections, is also delayed. The hippocampal formation experiences a reduction in the number of granular cells and mossy fibers. In the cerebellum, hypothyroidism arrests the maturation of the Purkinje cells and delays the migration of the granular cells to the internal granular layer. In the striatum, hypothyroidism delays the accumulation of the medium-spiny GABAergic neurons, the principal cells of the striatum. Parvalbumin interneurons in the cerebral and cerebellar cortices are also affected. Thyroid hormone induces extensive remodeling during cochlear and retinal maturation. Contrary to expectations, receptor-deficient mice often do not exhibit these alterations, while the expression of mutant receptors with impaired T3 binding results in hypothyroid features. In rodents, the effects of thyroid hormones are most prominent during the postnatal period. Conversely, in humans, the second trimester of pregnancy is a crucial period for neural development. The coordinated development of the thyroid hormone signaling system, encompassing brain T3 and the ontogenesis of receptors, deiodinases, and regulated genes, closely aligns with late maturational processes. This intricate interplay underscores the significance of thyroid hormones in shaping the structural and functional aspects of the developing brain.