Thyroid Hormone Transporters MCT8 and OATP1C1 are Expressed in Projection Neurons and Interneurons of Basal Ganglia and Motor Thalamus in the Adult Human and Macaque Brain

Abstract

Monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1) are thyroid hormones (TH) transmembrane transporters relevant for the availability of TH in neural cells, crucial for their proper development and function. Mutations in MCT8 or OATP1C1 result in severe disorders with dramatic movement disability related to alterations in basal ganglia motor circuits. Mapping the expression of MCT8/OATP1C1 in those circuits is necessary to explain their involvement in motor control. We studied the distribution of both transporters in the neuronal subpopulations that configure the direct and indirect basal ganglia motor circuits using immunohistochemistry and double/multiple labeling immunofluorescence for TH transporters and neuronal biomarkers. We found their expression in the medium-sized spiny neurons of the striatum (the receptor neurons of the corticostriatal pathway), and in various types of its local microcircuitry interneurons, including the cholinergic. We also demonstrate the presence of both transporters in projection neurons of intrinsic and output nuclei of the basal ganglia, motor thalamus and nucleus basalis of Meynert, suggesting an important role of MCT8/OATP1C1 for modulating the motor system. Our findings suggest that a lack of function of these transporters in the basal ganglia circuits would significantly impact motor system modulation, leading to clinically severe movement impairment.

Thyroid hormone action in adult neurogliogenic niches: the known and unknown

“…Expression of some TH-availability regulators was first reported in the striatum more than 40 years ago, with evidence of striatal DIO2 and DIO3 activity among the highest in the rodent brain ( 169 ). However, we had to wait until the present century to unravel the local expression of THTs, such as MCT8 and OATP1C1, both in mice, non-human primates, and humans, with a particularly high expression of OATP1C1 ( 170 – 172 ). Indeed, our recent work described the expression of both transporters in striatal motor neuron circuitry, as well as in pericytes in the primate striatum, implying the importance of THs in this area ( 172 ).…”

“…However, we had to wait until the present century to unravel the local expression of THTs, such as MCT8 and OATP1C1, both in mice, non-human primates, and humans, with a particularly high expression of OATP1C1 ( 170 – 172 ). Indeed, our recent work described the expression of both transporters in striatal motor neuron circuitry, as well as in pericytes in the primate striatum, implying the importance of THs in this area ( 172 ). Moreover, in rats, thyroidectomy and subsequent depletion of THs in the striatal area have been demonstrated to induce a number of transcriptomic changes ( 173 ).…”