Abstract
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.
Keywords: Basal ganglia, Cajal-Retzius cells, Cerebellum, Cerebral cortex, Cochlea, Cones, Cortical layering, Cortical plate, Deiodinases, Granular cells, Hair cells, Hippocampus, Interneurons, Neocortex, Nuclear receptors, Purkinje cells, Pyramidal cells, Radial glial cells, Retina, Rods, Subplate.
