Thyroid hormone is essential for brain development and brain function in the adult. During development, thyroid hormone acts in a spatial and temporal-specific manner to regulate the expression of genes essential for normal neural cell differentiation, migration, and myelination. In the adult brain, thyroid hormone is important for maintaining normal brain function. Thyroid hormone excess, hyperthyroidism, and thyroid hormone deficiency, hypothyroidism, are associated with disordered brain function, including depression, memory loss, impaired cognitive function, irritability, and anxiety. Adequate thyroid hormone levels are required for normal brain function. Thyroid hormone acts through a cascade of signaling components: activation and inactivation by deiodinase enzymes, thyroid hormone membrane transporters, and nuclear thyroid hormone receptors. Additionally, the hypothalamic-pituitary-thyroid axis, with negative feedback of thyroid hormone on thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) secretion, regulates serum thyroid hormone levels in a narrow range. Animal and human studies have shown both systemic and local reduction in thyroid hormone availability in neurologic disease and after brain trauma. Treatment with thyroid hormone and selective thyroid hormone analogs has resulted in a reduction in injury and improved recovery. This article will describe the thyroid hormone signal transduction pathway in the brain and the role of thyroid hormone in the aging brain, neurologic diseases, and the protective role when administered after traumatic brain injury. © 2021 American Physiological Society. Compr Physiol 11:1-21, 2021.
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