Thyroid Hormone Transporters Mct8 and Oatp1c1 Have Distinct Actions in Adult Hippocampal Neurogenesis in Murine

Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) cause Allan-Herndon-Dudley Syndrome, a severe type of psychomotor impairment, whereas mutations in another TH transporter, organic anion transporting polypeptide 1c1 (OATP1C1), cause juvenile neurodegeneration. These illnesses suggest that TH transporters play critical roles in CNS function. We recently identified Mct8 in adult hippocampus progenitors and mature granule cell neurons, as well as cell-autonomous and indirect Mct8 needs in adult hippocampal neurogenesis. We wanted to see if Oatp1c1 is engaged in the hippocampus neurogenic process together with Mct8.

In the dentate gyrus, we found Oatp1c1 gene expression activity and transcripts in subsets of progenitors, neurons, and niche cells. In 6-month-old Oatp1c1ko and Mct8/Oatp1c1 double knockout (M/Odko) mice, the absence of Oatp1c1 resulted in increased neuroblast and decreased immature neuron counts. Mct8ko and M/Odko mice had lower EdU-label retention, confirming Mct8’s role in neuron development. In the open field arena, however, there was no significant effect of Oatp1c1 deletion on granule cell neuron generation or anxiety-like behaviour. Our findings support the notion that unique activities of each TH transporter are necessary at various times to guarantee adequate adult hippocampus regeneration.

Author(s): Erica Melena*

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