IMPACT OF THYROID HORMONE TRANSPORTERS MCT8 AND OATP1C IN STEM CELL NICHE CELLS ON ADULT HIPPOCAMPAL NEUROGENESIS

In adults, thyroid hormone (TH) is critical for the maintenance of brain functions, and TH deficiency is associated with anxiety, depression, and cognitive impairments. TH governs adult hippocampal neurogenesis (AHN), the continuous generation of new neurons from neural stem cells in the hippocampal subgranular zone, which is essential for cognitive flexibility and emotional regulation. Cellular uptake of TH is mediated by specific membrane transporters, such as monocarboxylate transporter 8 (Mct8) and organic anion transporting polypeptide 1C1 (Oatp1c1). Our previous work demonstrated that these transporters are expressed at distinct stages of the murine neurogenic lineage and their absence impairs the generation of new hippocampal neurons in mice. Moreover, our findings pointed out the existence of non–cell-autonomous effects of Mct8/Oatp1c1 within the neurogenic niche. Astrocytes, endothelial cells and neurons are key components of the neurogenic niche and express both transporters. Here, we investigated whether Mct8 and Oatp1c1 exert effects on AHN through their expression in neurons. To this end, we generated conditional Mct8/Oatp1c1 double-knockout mice with targeted deletion of both TH transporters in either glutamatergic (using Vglut2-Cre) or GABAergic neurons (using Gad2-Cre). AHN was assessed by immunofluorescence analysis of progenitor cell development and neuronal maturation, along with hippocampus-dependent behaviors evaluations. Deletion of both transporters in both neuron types did not affect AHN, anxiety-like behavior, or recognition memory. This indicates that Mct8 and Oatp1c1-mediated TH flux in neurons does not influence AHN. A similar approach is currently applied employing astrocyte- and endothelial-specific knockouts to determine the role of TH transporters therein.