Thyroid hormone (TH) transport routes in the fetal brain

Abstract

In the 2013 MCT8 symposium we presented data on the pathology of MCT8-deficient brain, showing histological alterations compatible with impaired TH action during neural development. Mechanisms of TH transport and their interaction with deiodinases in the developing human brain are poorly understood. In rodents Mct8 is present in the BBB, the neural cell membranes, and the choroid plexus, and Oatp1c1 is present in the BBB, the astrocytes, the choroid plexus and the ventricular surface. D2 is present in glial cells and D3 in neurons. Understanding how all these factors interact is essential to understand the pathophysiological mechanisms in MCT8 deficiency. In this presentation we will show that in the human fetus MCT8 is expressed in brain vessels, and also in the ependimocytes and the radial glia. D3 immunoreactivity is also present in the radial glia. DIO2 mRNA is expressed in the developing cortex, probably in the radial glia, but this awaits confirmation. The data suggest additional transport routes whereby the radial glia regulates the amounts of T4 and T3 available to the developing cortex. Future directions will include the analysis of this process in more detail by correlating the expression of transporters and deiodinases in the developing human brain at different stages of maturation, and looking for its correlate in the mouse brain.