Distinct actions of the thyroid hormone transporters Mct8 and Oatp1c1 in murine adult hippocampal neurogenesis

Mayerl, Steffen, Alcaide Martin, Andrea, Bauer, Reinhard, Schwaninger, Markus, Heuer, Heike and ffrench-Constant, Charles (2022) Distinct actions of the thyroid hormone transporters Mct8 and Oatp1c1 in murine adult hippocampal neurogenesis. Cells, 11 (3). ISSN 2073-4409

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Abstract

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) result in Allan-Herndon-Dudley Syndrome, a severe form of psychomotor retardation, while inactivating mutations in another TH transporter, organic anion transporting polypeptide 1c1 (OATP1C1), are linked to juvenile neurodegeneration. These diseases point to essential roles for TH transporters in CNS function. We recently defined the presence of Mct8 in adult hippocampal progenitors and mature granule cell neurons and unraveled cell-autonomous and indirect requirements for Mct8 in adult hippocampal neurogenesis. Here, we investigated whether Oatp1c1 is involved in the hippocampal neurogenic process in concert with Mct8. We detected Oatp1c1 gene expression activity and transcripts in subsets of progenitors, neurons and niche cells in the dentate gyrus. Absence of Oatp1c1 resulted in increased neuroblast and reduced immature neuron numbers in 6-month-old Oatp1c1ko and Mct8/Oatp1c1 double knockout (M/Odko) mice. Reduced EdU-label retention in Mct8ko and M/Odko mice confirmed the impact of Mct8 on neuron formation. In contrast, no significant effect of Oatp1c1 loss on granule cell neuron production and anxiety-like behavior in the open field arena were seen. Together, our results reinforce that distinct actions of each TH transporter are required at multiple stages to ensure proper adult hippocampal neurogenesis.

Item Type: Article
Additional Information: Funding Information: Funding: This work was supported by grants of the DFG to S.M. (MA7212/2 as well as the CRC/TR296-P19) and to H.H. and M.S. (CRC/TR296-P01). C.ff.C. received funding from a Wellcome Trust Senior Investigator award (104783/Z/14/Z) and from the BBSRC (BB/L00402X/1).
Uncontrolled Keywords: adult hippocampal neurogenesis,allan-herndon-dudley syndrome,mct8,oatp1c1,slc16a2,slco1c1,thyroid hormone,medicine(all) ,/dk/atira/pure/subjectarea/asjc/2700
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 10 Mar 2022 14:30
Last Modified: 24 Mar 2022 15:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/83982
DOI: 10.3390/cells11030524

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