The role of thyroid hormone on functional organization in the cerebellum.

The thyroid hormone (L-triiodothyronine (T3), thyroxine (T4)) plays a critical role in cerebellar development. Circulating T4 preferentially crosses the blood-brain barrier through several amino acid transporters. Then, it is taken up by astrocyte to convert into T3, which is a bioactive ligand for nuclear thyroid hormone receptor (TR). Liganded TR regulates the expression of target genes that may play an important role in cerebellar development and function. Thus, thyroid hormone deficiency results in the change in neuronal excitability and aberrant neurotransmitter transport, which induces abnormal motor coordination, decreased locomotor activity, and increased anxiety. In addition to genomic action of the thyroid hormone, T4 alters actin polymerization and iodothyronine deiodinase activity in astrocyte through non-genomic pathway, which may also contribute to the normal brain development. Taken together, thyroid hormone regulates cerebellar development and plasticity through multiple signal transduction pathways.