Thyroid hormone and remyelination in adult central nervous system: a lesson from an inflammatory-demyelinating disease

Calzà, Laura; Fernández, Mercedes; Giuliani, Alessandro; D’Intino, Giulia; Pirondi, Stefania; Sivilia, Sandra; Paradisi, Mario Paglialunga; DeSordi, Nadia; Giardino, Luciana

doi:10.1016/j.brainresrev.2004.12.022

Cited by 48 publications

(40 citation statements)

References 83 publications

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“…58,59 Some studies have insisted that TH can affect the timing of OPC differentiation. 60 Others suggest that TH affects the secretion of neurotrophic factors. [61][62][63] However, a function for T3 in remyelination had not been shown and we explored this in our study.…”

Section: Th Promotes Remyelination During the Remission Periodmentioning

confidence: 99%

Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period

Zhang

Zhan

et al. 2015

Exp Biol Med (Maywood)

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Multiple sclerosis (MS) is a disease induced by demyelination in the central nervous system, and the remission period of MS is crucial for remyelination. In addition, abnormal levels of thyroid hormone (TH) have been identified in MS. However, in the clinic, insufficient attention has been paid to the role of TH in the remission period. Indeed, TH not only functions in the development of the brain but also affects myelination. Therefore, it is necessary to observe the effect of TH on remyelination during this period. A model of demyelination induced by cuprizone (CPZ) was used to observe the function of TH in remyelination during the remission period of MS. Through weighing and behavioral tests, we found that TH improved the physical symptoms of mice impaired by CPZ. Supplementation of TH led to the repair of myelin as detected by immunohistochemistry and western blot. In addition, a sufficient TH supply resulted in an increase in myelinated axons without affecting myelin thickness and g ratio in the corpus callosum, as detected by electron microscopy. Double immunostaining with myelin basic protein and neurofilament 200 (NF200) showed that the CPZ-induced impairment of axons was alleviated by TH. Conversely, insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of mitochondria. Furthermore, we found that an adequate supply of TH promoted the proliferation and differentiation of oligodendrocyte lineage cells by immunofluorescence, which was beneficial to remyelination. Further, we found that TH reduced the number of astrocytes without affecting microglia. Conclusively, it was shown that TH alleviated demyelination induced by CPZ by promoting the development of oligodendrocyte lineage cells and remyelination. The critical time for remyelination is the remission period of MS. TH plays a significant role in alleviating demyelination during the remission period in the clinical treatment of MS.

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Section: Th Promotes Remyelination During the Remission Periodmentioning

confidence: 99%

Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period

Zhang

Zhan

et al. 2015

Exp Biol Med (Maywood)

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“…There are two circulating thyroid hormones: thyroxin (T 4 ) and T 3 , and their action is transduced by thyroid hormone receptors (TRs), expressed in different cell types, including precursors and mature oligodendrocytes. The effects of T 4 hormone on remyelination were recently reported in an EAE rat model of immuno-inflammatory demyelination in which a severe oligodendrocyte population depletion is not clear (Calza et al, 2002;Fernandez et al, 2004;Calzà et al, 2005). Because the T 4 will be further converted in T 3 in the organism, and because the TRs affinity is much higher for T 3 , we chose to use directly T 3 hormone injections as stimulating therapy leading to remyelination in chronically demyelinated mouse brain lesions.…”

Section: Remyelination Induced By T 3 -Based Therapymentioning

confidence: 99%

Recovery from Chronic Demyelination by Thyroid Hormone Therapy: Myelinogenesis Induction and Assessment by Diffusion Tensor Magnetic Resonance Imaging

Harsan¹,

Steibel²,

Zaremba³

et al. 2008

J. Neurosci.

146

126

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The failure of the remyelination processes in multiple sclerosis contributes to the formation of chronic demyelinated plaques that lead to severe neurological deficits. Long-term cuprizone treatment of C57BL/6 mice resulted in pronounced white matter pathology characterized by oligodendrocyte depletion, irreversible demyelination and persistent functional deficits after cuprizone withdrawal. The use of a combination of in vivo diffusion tensor magnetic resonance imaging (DT-MRI) and histological analyses allowed for an accurate longitudinal assessment of demyelination. Injection of triiodothyronine (T 3 ) hormone over a 3 week interval after cuprizone withdrawal progressively restored the normal DT-MRI phenotype accompanied by an improvement of clinical signs and remyelination. The effects of T 3 were not restricted to the later stages of remyelination but increased the expression of sonic hedgehog and the numbers of Olig2 ϩ and PSA-NCAM ϩ precursors and proliferative cells. Our findings establish a role for T 3 as an inducer of oligodendrocyte progenitor cells in adult mouse brain following chronic demyelination.

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“…Consistent with these fi ndings, TH also aff ects myelination and remyelination. Thus it has been shown in vivo in diff erent demyelination and MS animal models that TH enhances and accelerates remyelination by promoting neural progenitor diff erentiation into OPCs and oligodendrocytes (Calza et al, 2002;Calzà et al, 2005;Franco et al, 2008). In conclusion, TH induces OPC diff erentiation, maturation and enhances remyelination.…”

Section: The Oligodendrogenic Program: Molecular Mo-dulation Of Oligomentioning

confidence: 99%

Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis

Rivera¹,

Aigner²

2012

Biol. Res.

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Multiple sclerosis (MS) is a demyelinating immune-mediated disease of the central nervous system (CNS). It is the most frequent neurological disease in young adults and aff ects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of infl ammatory lesions in the CNS, but with only temporary and limited success. Despite the presence of endogenous oligodendroglial progenitors (OPCs) and of spontaneous remyelination, at least in early MS its levels and its qualities are apparently insuffi cient for a sustained endogenous functional repair. Therefore, novel MS therapies should consider not only immunemodulatory but also myelin repair activities. Mesenchymal stem cells (MSCs) represent an attractive alternative to develop a cell-based therapy for MS. MSCs display stromal features and exert bystander immunemodulatory and neuroprotective activities. Importantly, MSCs induce oligodendrocyte fate decision and diff erentiation/maturation of adult neural progenitors, suggesting the existence of MSC-derived remyelination activity. Moreover, transplanted MSCs promote functional recovery and myelin repair in diff erent MS animal models. Here, we summarize the current knowledge on endogenous mechanisms for remyelination and proposed autologous MSC therapy as a promising strategy for MS treatment.

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Thyroid hormone and remyelination in adult central nervous system: a lesson from an inflammatory-demyelinating disease

Cited by 48 publications

References 83 publications

Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period

Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period

Recovery from Chronic Demyelination by Thyroid Hormone Therapy: Myelinogenesis Induction and Assessment by Diffusion Tensor Magnetic Resonance Imaging

Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis

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