Abstract
Thyroid hormone plays a critical role in cerebellar development. Its deficiency results in various abnormalities, including reduced dendritic arborization of Purkinje cells, prolonged proliferation and delayed migration of external granule cells, and decreased synaptogenesis between Purkinje and granule cells. Such abnormal development cannot be rescued unless thyroid hormone is replaced within first two weeks of postnatal life in rodents. Thyroid hormone acts by binding to nuclear thyroid hormone receptor (TR) that is a ligand dependent transcription factor, which binds to thyroid hormone response element (TRE) located at the promoter region of its target gene. TR further recruits cofactors such as SRC-1, which is also strongly expressed in cerebellum. It regulates transcription of target genes only during first two weeks of postnatal life in rodents. Target gene includes RORα, neurotrophic factors and myelin basic proteins. Among such genes, RORα may play a critical role in TR-mediated cerebellar development. Cerebellar phenotype and alteration of neurotrophin expression of mutant mouse (staggerer) harboring RORα mutation is similar to that of hypothyroid mouse. Furthermore, although RORα augments TR-mediated transcription, staggerer type mutant RORα does not have such action. These results indicate that RORα may play a major role in TR-mediated cerebellar development. [J Physiol Sci. 2007;57 Suppl:S43]
