Absence of thyroid hormone transporters Mct8/Oatp1c1 causes distinct spinal cord alterations in adult female mice.

Thyroid hormone (TH) is critical for a normal development of the nervous system and the maintenance of adult CNS functions. As a prerequisite of its cellular action, TH is taken up across CNS barriers and further into target cells by specialized transporters such as the monocarboxylate transporter 8 (MCT8). MCT8 mutations result in a severe form of psychomotor retardation that is accompanied by a prominent neuromotor component. Despite its central involvement in the relay of motor commands and somatosensation, potential contributions of spinal cord abnormalities to the MCT8 phenotype are elusive. In mice, a MCT8 deficiency-like phenotype can be induced by the combined deletion of Mct8 and the T4-specific organic anion transporting polypeptide 1c1 (Oatp1c1). Here, we first studied the expression pattern of Mct8 and Oatp1c1 in adult murine spinal cord sections by in situ hybridization and immunofluorescence. We detected Mct8 expression in endothelial cells and motoneurons, while Oatp1c1 was found in the endothelium and glia cells, thus resembling their pattern in the brain. Global absence of Mct8/Oatp1c1 results in reduced TH concentrations and affected TH signaling in the spinal cord in adult female mice. Immunofluorescence analyses and RNA sequencing pointed to unaltered myelination and cholinergic neurotransmission in Mct8/Oatp1c1 deficiency, whereas genes involved in sensory processing appeared differentially regulated. Finally, we demonstrated increased thermal sensitivity in the tail immersion test in adult female Mct8/Oatp1c1 deficient mice. Together, our results underscore a critical role of Mct8/Oatp1c1-mediated TH signaling for proper spinal cord function.