Cortical pyramidal cells express thyroid hormone transporters MCT8 and OATP1C1 in human and monkey brain

Resumen del trabajo presentado en el 19th National Meeting of the Spanish Society of Neuroscience, celebrado en LLeida (España) del 03 al 05 de noviembre de 2021.Monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1) are thyroid hormone (TH) transmembrane transporters that play a crucial role in the availability of systemic THs for neural cells allowing their appropriate development and function. MCT8 mutations are the underlying reason of Allan-Herndon-Dudley syndrome which expresses a dramatic motor disfunction. This study aims to analyze the presence of these two proteins at the cellular level in the monkey and human cerebral cortex. We analyzed the distribution of these two transporters in the cerebral cortex of 30-50 µm floating frozen cerebral cortex sections taken from three cynomolgus monkeys and four adult humans by Nissl staining, immunohistochemistry, double labeling immunofluorescent and immunohistochemistry combined with NADPH-diaphorase histochemistry. OATP1C1 is expressed in pyramidal neurons in layers II, III, V, and VI in both monkey and human brain, as evidenced by colocalization with RC3/Neurogranin. Non-colocalization with NADPHdiaphorase implies that OATP1C1 is not expressed in multipolar, bitufted and stellate NOSexpressing GABAergic interneurons in the cortex. MCT8 distribution is similar to that of OATP1C1 in monkey and human brain, although the intensity of its signal is lower. Interestingly, Cajal-Retzius like cells expressing OATP1C1 are observed in layer I. OATP1C1 and MCT8 immunostained cells with very small soma and large processes compatible with astrocyte morphology are found in the subcortical white matter in close relation to vessels. MCT8 is also expressed in the endothelial cells of the different size vessels and capillaries throughout the monkey and human cortex, while OATP1C1 is occasionally observed in the endothelium of large and medium-sized vessels. Our results demonstrate the abundance of MCT8 and OATP1C1 TH transporters in the long and short projection pyramidal cortical neurons and in the astrocyte-vessel complexes in adult human and nonhuman primates, which suggest their critical position in the efferent cortical motor system