Combined deletion of Mct8 and Dio2 impairs SVZ neurogliogenesis and olfactory function in adult mice

Within the adult mouse subventricular zone (SVZ), neural stem cells (NSCs) produce neuroblasts and oligodendrocyte precursor cells (OPCs). T3, the active thyroid hormone, influences renewal and commitment of SVZ progenitors. However, how regulators of T3 availability affect these processes is less understood. Using Mct8/Dio2 knockout mice, we investigated the role of MCT8, a TH transporter, and DIO2, the T3-generating enzyme, in regulating adult SVZ-neurogliogenesis. Single-cell RNA-Seq revealed Mct8 expression in various SVZ cell types in WT mice, while Dio2 was enriched in neurons, astrocytes, and quiescent NSCs. The absence of both regulators in the knockout model dysregulated gene expression, increased the neuroblast/OPC ratio and hindered OPC differentiation. Immunostainings demonstrated compromised neuroblast migration reducing their supply to the olfactory bulbs, impairing interneuron differentiation and odor discrimination. These findings underscore the pivotal roles of MCT8 and DIO2 in neuro- and oligodendrogenesis, offering targets for therapeutic avenues in neurodegenerative and demyelinating diseases. [Display omitted] •MCT8 and DIO2 are pivotal for proper neuro- oligodendrogenesis in the adult murine SVZ.•Lack of MCT8 and DIO2 alters the transcriptomic landscape in the adult SVZ.•MCT8 and DIO2 absence leads to decreased migration from SVZ-derived progenitors.•MCT8 and DIO2 absence leads to an altered neuroarchitecture in the olfactory bulbs.•Lack of MCT8 and DIO2 leads to reduced olfactory memory and discrimination.