Oligodendroglial Lineage Cells in Thyroid Hormone-Deprived Conditions

Figure 1

Hypothyroid state within the CNS leads to cellular hypothyroidism in oligodendrocytes. In the euthyroid state, functional MCT8 expressed on oligodendrocyte precursors (OPCs) is able to transport thyroid hormone (T₃) across the plasma membrane promoting their differentiation and maturation. Normal myelination subsequently occurs. When MCT8 is dysfunctional due to various points or frameshift mutations, or in the context of neuroinflammation, intracellular T₃ transport is impeded, as a result of dysfunctional MCT8. This results in a profound hypothyroid state in OPCs, leading to their stalled differentiation, or indeed apoptosis, with the eventual neurobiological result being hypomyelination and the clinical outcome being neurodegeneration and cognitive decline.