Thyroid Hormone Receptor Mutation and Neurodevelopment

Jens Mittag*

*Corresponding author for this work
1 Citation (Scopus)


Insufficient levels of thyroid hormone during development are detrimental for the brain, and the resulting defects can last into adulthood. Likewise, mutations in the nuclear thyroid hormone receptors severely interfere with brain development. Thyroid hormone receptor α1, which is the major receptor isoform in almost all neurons, plays the pivotal role in mediating the effects of thyroid hormone in the brain; however, some distinct functions are also governed by thyroid hormone receptor β. On the neuroanatomical level, impaired thyroid hormone receptor signaling leads to reduced myelination and branching, decreased synaptogenesis, and problems in neuronal migration, often affecting the number of neurons in certain brain areas. Particularly sensitive to changes in thyroid hormone signaling during development are neurons containing the neurotransmitter γ-aminobutyric acid (GABA) in the cortex, hippocampus, cerebellum, or hypothalamus. The anatomical defects are accompanied by consequent changes in motoric functions, memory, spatial navigation, or alterations in endocrine and autonomic homeostasis. Although transgene animal models for mutations in thyroid hormone receptors have greatly contributed in dissecting the distinct roles of thyroid hormone receptor isoforms in brain development and function, only a few cellular and molecular targets have been thoroughly characterized to date. This chapter summarizes the current knowledge on thyroid hormone receptors in neurodevelopment.

Original languageEnglish
Title of host publicationContemporary Clinical Neuroscience
Number of pages15
PublisherSpringer Nature Singapore
Publication date2016
Publication statusPublished - 2016

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