Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit inthe developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.
Bibliographical noteFunding Information:
This work was supported, in part, by an NIH R01 DK054060 grant and a Grant-in-Aid from the University of Minnesota Graduate School. Figures 1 and 2 were created using ScienceSlides 2006 software from Visiscience.
- Granule cell
- Purkinje cell
- Thyroid hormone