The role of thyroid hormone in fetal and neonatal brain development

Abstract

Purpose of reviewTo understand how thyroid hormone regulates brain development it is important to identify thyroid hormone-responsive brain genes; determine how regulated expression of these genes affects brain cell development, physiology, and function; and determine how these physiologic changes affect brain function. The authors summarize recent studies contributing to the understanding of these processes and discuss important new studies that assess thyroid hormone metabolism in the developing brain. Recent findingsSpecific thyroid hormone transporters are expressed in the developing brain. Recent data suggest that regulated expression of these transporters may control brain thyroid hormone influx and efflux. Additional data support a role for deiodinases in controlling local iodothyronine concentrations in the developing brain. A series of recent reports assesses the role of thyroid hormone in oligodendrocyte development and axonal myelination. These data provide a cellular and molecular explanation for the hypomyelination observed in neonates that have developed in a hypothyroid state. The cerebellar Purkinje cell is another well-described target of thyroid hormone in the developing brain. A recent study provides evidence that thyroid hormone acts directly on the Purkinje cell to regulate dendritic arborization. Finally, important new data provide insight regarding the functional effects of thyroid hormone deficiency on neuronal activity. Summary Recent work has provided exciting new insights regarding the mechanisms controlling thyroid hormone action in the developing brain. It seems likely that regulation of thyroid hormone metabolism and transport during brain development is a critically important mechanism of control. Additionally, important new findings have furthered our understanding of the structural and physiologic effects of thyroid hormone deficiency and excess on brain cell function.

Thyroid hormone and cerebellar development

“…Intellectual impairment occurs in humans when a congenitally hypothyroid infant develops in the context of low circulating TH levels, or when both the maternal and fetal supply of these hormones has been inadequate during pregnancy (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Although more rare than hypothyroidism, hyperthyroidism during infancy can also lead to significant structural and intellectual deficits.…”

“…Additionally, TH deficiency leads to abnormalities in other cell types located in the cerebellum, including astrocytes and Golgi epithelial cells (altered process formation (48,49)) and basket cells (reduced basket cell numbers in both hypo-and hyperthyroidism (5)). Finally, myelination is reduced under hypothyroidism as the developing oligodendrocyte is a direct target of TH action (22,(50)(51)(52)(53).…”

Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8

“…Even more importantly, it is crucially involved in the maturation and function of the CNS (1-3). Absence of thyroid hormone during pre- and early postnatal periods affects a variety of processes, such as neuronal migration and differentiation as well as myelination, thus leading to a vast array of clinical manifestations (4,5). In humans, fetal and/or neonatal thyroid hormone deficiency results in the syndrome of cretinism, a disorder characterized by severe mental retardation, neurological deficits (e.g., movement disorders, spasticity, and speech problems), as well as hearing impairment.…”

Factors and Mechanisms of Thyroid Hormone Activity in the Brain: Possible Role in Recovery and Protection

“…They influence neurogenesis, neuronal and glial cell differentiation and migration, synaptogenesis, and myelination. Thyroid hormone deficiency may severely affect the brain during fetal and postnatal development, causing retarded maturation, intellectual deficits, and neurological impairment [1][2][3][4].…”