TABLE 1.
Summary of thyroid hormone effects in MS models.
| Study | Species | Model | Treatment | Effects |
| (Calza et al., 2002) | ♀ rats | EAE | s.c. T4 | Proliferating cells SVZ + SC ↓ OPC + Mature OL markers ↑ NGF content ↑ |
| (Fernandez et al., 2004) | ♀ rats | EAE | s.c. T4 | OPC + Mature OL markers ↑ Myelin sheath reassembly ↑ Relapse severity ↓ Axon morphology ↑ |
| (Franco et al., 2008) | rats | CPZ | s.c. T3 | Proliferating cells SVZ ↓ OPC cycle exit ↑ SVZ TRβ expression ↑ OL markers CC ↑ Remyelination of the CC |
| (Harsan et al., 2008) | ♀ mice | CPZ | i.p. T3 | Proliferating cells SVZ ↑ OPCs & Neuroblasts ↑ Myelinated axons ↑ MRI WM status CC & Cb ↑ Motor performance ↑ |
| (Fernández et al., 2009) | Neurospheres derived from EAE rats | / | T3 | Proliferation ↓ OPC genesis ↑ OL maturation ↑ |
| (D’Intino et al., 2011) | ♂ + ♀ marmosets | EAE | s.c. T3 | OPC + Mature OL markers ↑ Disability score ↓ Preservation myelin sheaths ↑ Inflammation ↓ Normalization tissue TH metabolism |
| (Dell’Acqua et al., 2012) | ♀ rats | EAE | s.c. T3 | Disability score ↓ Neurophysiological parameters ↑ Remyelination ↑ Nerve impulse propagation ↑ Neurofilament levels normalized TRα1 + TRβ expression normalized |
| (Castelo-Branco et al., 2014) | ♂ + ♀ rats | EAE | s.c. T4 + VA | Myelin loss ↓ OPC + Mature OL markers = Inflammation ↓ Clinical signs ↑ |
| (Zhang et al., 2015) | mice | CPZ | i.p. T3 | OPC proliferation and differentiation ↑ Remyelination in the CC Myelinated axons ↑ Myelin thickness/g-ratio = MRI WM status ↑ Clinical signs ↑ |
| (El-Tahry et al., 2016) | ♂ rats | CPZ | s.c. T3 | Mature OL markers ↑ Myelinated axons ↑ Remyelination in the CC |
| (Fernández et al., 2016) | OPC-enriched cell culture | Cytokine exposure | IOP + T4 + T3 | OPC differentiation recovery Klf9 gene expression normalized |
| (Remaud et al., 2017) | ♂ mice | CPZ | MMI during CPZ exposure followed by T4 + T3 | SVZ-OPCs ↑ g-ratio ↓ (normal myelin thickness) Functional remyelination in the CC |
| (Shultz et al., 2017) | ♀ rats | CCI | Local hydroxygel-based T3 delivery | Oligodendrogenesis in vitro ↑ OL maturation in vitro ↑ |
| (Hartley et al., 2019) | OPCs from P7 rats | T3 sobetirome | Sobetirome mimics T3 action Klf9, Mbp, Hr expression ↑ |
|
| ♂ mice | CPZ | i.p. T3 or i.p. sobetirome | Remyelination in the CC Mature OLs ↑ Myelinated axons ↑ | |
| ♂ mice | Lysolecithin | i.p. T3 or i.p. sobetirome | ||
| ♂ + ♀ iCKO-Myrf mice | / | T4 + T3 or PTU sobetirome or Sob-AM2 chow | Both had adverse effects on long-term remyelination T4 + T3 OPCs + OLs ↓ OL maturation ↑ Myelinated axons ↑ Remyelination ↑ WM MRI status ↑ Motor performance ↑ |
Abbreviations: Cb, cerebellum; CC, corpus callosum; CCI, cervical contusion injury; CPZ, cuprizone; EAE, experimental autoimmune encephalomyelitis; Hr, hairless; IOP, iopanoic acid; i.p., intraperitoneal; Klf9, Krüppel-like factor 9; MBP, myelin basic protein; MMI, methimazole; MRI, magnetic resonance imaging; NGF, neural growth factor; NSC, neural stem cell; OL, oligodendrocyte; OPC, oligodendrocyte precursor cell; PTU, propylthiouracil; s.c., subcutaneous; SC, spinal cord; SVZ, subventricular zone; TH, thyroid hormone; TR, thyroid hormone receptor; VA, valproic acid; WM, white matter.