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

Affiliation
Department of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany;(A.A.M.);(H.H.)
Mayerl, Steffen;
Affiliation
Department of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany;(A.A.M.);(H.H.)
Alcaide Martin, Andrea;
GND
120228920
ORCID
0000-0002-4294-3758
Affiliation
Institute of Molecular Cell Biology, Jena University Hospital, 07745 Jena, Germany;
Bauer, Reinhard;
GND
1028374909
ORCID
0000-0002-4510-9718
Affiliation
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23562 Lübeck, Germany;
Schwaninger, Markus;
ORCID
0000-0001-7094-6959
Affiliation
Department of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany;(A.A.M.);(H.H.)
Heuer, Heike;
Affiliation
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK;
ffrench-Constant, Charles

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.

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