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Thyroid hormone receptors in brain development and function.

Juan Bernal1

  • 1Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Autonomous University of Madrid, Spain. jbernal@iib.uam.es

Nature Clinical Practice. Endocrinology & Metabolism
|February 23, 2007
PubMed
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Thyroid hormone receptors (TRs) are crucial for brain development and function. Their activity, even without hormones, significantly impacts brain maturation and adult behavior.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Developmental Biology

Background:

  • Thyroid hormones are vital for mammalian brain development, influencing neural cell migration, differentiation, synaptogenesis, and myelination.
  • Thyroid hormone receptors (TRs) mediate these effects by regulating gene expression.
  • Several TR isoforms, including TRalpha1, are expressed in the brain, encoded by THRA and THRB genes.

Purpose of the Study:

  • To review the critical role of thyroid hormone receptors (TRs) in brain maturation.
  • To explore the function of TRs in both developing and adult mammalian brains.

Main Methods:

  • Review of existing literature on thyroid hormone receptors and brain development.
  • Analysis of studies involving TR isoform expression and genetic manipulation (e.g., TRalpha1 deletion, dominant-negative mutants) in rodents.

Related Experiment Videos

  • Examination of the impact of TR activity on neural development and behavior.

    • Main Results:

    • Maternal thyroid hormones are crucial for fetal brain development before midgestation, aligning with TR ontogeny.
    • TRalpha1 deletion in rodents does not fully mimic hormone deprivation and can paradoxically prevent hypothyroidism effects, suggesting unliganded TR activity is important.
    • Expression of a dominant-negative mutant TR impairs cerebellar development and motor performance, highlighting the significance of functional TRs.
    • TRalpha1 deletion or dominant-negative TR expression in adult mice leads to anxiety and hippocampal changes.

    Conclusions:

    • Thyroid hormone receptors play a multifaceted role in brain development and function, extending beyond simple hormone mediation.
    • Unliganded TR activity is a significant factor in the detrimental effects of hypothyroidism on the developing brain.
    • TRs are implicated in adult brain function, with alterations leading to behavioral and morphological changes.