Triiodothyronine is a survival factor for developing oligodendrocytes

Jones, Sidney A.; Jolson, Dawn M.; Cuta, Kristin K; Mariash, Cary N.; Anderson, Grant W.

doi:10.1016/s0303-7207(02)00296-4

Cited by 77 publications

(58 citation statements)

References 60 publications

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“…No effects on MBP expression actually were found in this and previous studies in nonpathological rats (24,50). Finally, TH also affects survival of developing oligodendrocytes, also overcoming proapoptotic effects mediated by the inflammatory cytokines tumor necrosis factor ␣ and interleukin 1 (53).…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Fernández

Giuliani

Pirondi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

126

101

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Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.e., experimental allergic encephalomyelitis in congenic female Dark Agouti rats immunized with complete guinea pig spinal cord. Thyroid hormone, when administered during the acute phase of the disease, increases expression of platelet-derived growth factor ␣ receptor, restores normal levels of myelin basic protein mRNA and protein, and allows an early and morphologically competent reassembly of myelin sheaths. Moreover, thyroid hormone exerts a neuroprotective effect with respect to axonal pathology.neuroprotection ͉ multiple sclerosis ͉ oligodendrocyte precursor cells ͉ axonal pathology ͉ rat M ultiple sclerosis (MS) is a disorder of the central nervous system (CNS) that manifests as acute focal inflammatory demyelination with limited remyelination, usually culminating in chronic multifocal sclerotic plaques (1). Early axonal injury and loss followed by neuron distress (2) and death (3) occur in MS (4-6), accounting for brain and spinal cord atrophy. Irreversible axonal damage is an essential cause of nonremitting sensory, motor, and cognitive disabilities in MS (7). Although remyelination occurs in most experimental models of demyelination, this beneficial process is undoubtedly inadequate in MS. The reasons for this inadequacy are unknown, also because the oligodendrocyte precursor cells (OPCs), the cell population that is considered to be the most important source of remyelinating oligodendrocytes in the adult CNS (8-10), are present in early (fresh) demyelinating lesions in MS (11, 12).There are many possible speculative explanations for remyelination failure in MS (9, 10), including quantitatively inadequate recruitment and͞or differentiation of OPCs (13); axons not receptive to remyelination (14); and inappropriate support of growth factors by astrocytes and͞or other inflammatory cells (15), such as the extracellular microenvironment with regard to matrix proteins and adhesion molecules (16).Because the number of oligodendrocytes is greater than before demyelination in early MS, meaning that new oligodendrocytes are generated (17), another possibility is that OPCs are unable to turn into myelinating oligodendrocytes in chronic MS. Thus, extensive studies are under way to identify factors involved in OPC differentiation during remyelination. It is generally accepted that the process of remyelination represents a recapitulation of myelination during development, and so the key factors affecting the developmental maturation of OPCs into myelinating oligodendrocytes also should favor remyelination in the adult CNS. It ...

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Section: Discussionmentioning

confidence: 99%

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Fernández

Giuliani

Pirondi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

126

101

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“…This comparative analysis was performed after cells were maintained in culture for 5 to 7 days under relatively basal culture conditions supplemented with growth factors (bFGF and T3) that are considered to promote cell survival and proliferation rather than differentiation. 24,25 A small proportion (5 to 10%) of the adult A2B5 ϩ cell population morphologically distinct from the CD68 microglia expressed NG2 ϩ , which is found later in the OLG progenitor lineage than is A2B5, showing the persistence of the progenitor characteristic on these cells. This population was smaller than in fetal A2B5 ϩ cells (10 to 20% of cells).…”

Section: Discussionmentioning

confidence: 99%

Distinctive Properties of Human Adult Brain-Derived Myelin Progenitor Cells

Ruffini

Arbour

Blain

et al. 2004

The American Journal of Pathology

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We used expression of the ganglioside A2B5 to isolate putative myelin progenitor cells from adult human central nervous system parenchyma and compared their phenotypic (expression of myelin lineage molecules) and functional (survival, proliferation) properties with mature oligodendrocytes (OLGs) derived from the same adult material and with A2B5 ؉ cells isolated from human fetal brain. A2B5 ؉ cells represented 3 to 5% of the total cell suspension derived from adult specimens. Results of protein (immunostaining) and RNA (polymerase chain reaction) analyses indicated that the adult A2B5 ؉ cells were more committed to the OLG lineage than their fetal counterparts while continuing to retain properties of progenitor cells compared to the postmitotic mature OLGs. Although the adult A2B5 ؉ cells retained the capacity to divide, albeit at a reduced rate compared to fetal A2B5 ؉ cells, they showed reduced survival and process outgrowth compared not only to fetal cells but also to mature OLGs. Our results confirm the presence of progenitor cells committed to the OLG lineage in the adult human central nervous system but raise the issues regarding the intrinsic capacity of these cells to contribute to the process of remyelination that may be necessary during demyelinating diseases. Recovery from relapses in multiple sclerosis (MS) is attributed at least in part to the extent of remyelination observed in early MS lesions. 16 and PLP ϩ pre-OLGs. 17 These cells do not however appear to be overrepresented nor are they consistently proliferating in the lesions. In late chronic MS lesions, where remyelination is less widespread than in early lesions, the number of both progenitors and mature OLGs is decreased compared to early active lesions.Roy and colleagues, 18 reported that progenitor cells (ganglioside A2B5-positive) comprised 3 to 5% of the total cell population derived from human adult temporal lobe resections and could undergo a limited number of cell divisions in vitro. OLGs could be derived only from the A2B5 ϩ population, although this population could also give rise to neurons and astrocytes. 20 -22 The purpose of our current study was to compare phenotypic (myelin lineage gene expression) and functional (in vitro survival, cell cycling, and process formation) properties of the adult A2B5 ϩ cells with those of mature OLGs isolated from the same tissue samples. We further compared the properties of adult A2B5 ϩ cells with their fetal counterparts providing insight for the observation that, when compared to fetal A2B5 ϩ cells, transplanted adult A2B5 ϩ cells produce fewer surviving cells but among those a higher proportion contribute to myelination of the dismyelinated mouse mutants, shiverer mice. 19 -21 Our results demonstrate that the adult A2B5 ϩ cells retain properties of progenitor cells when compared to postmitotic mature human OLGs and are more committed to the OLG lineage than their fetal counterparts. Adult A2B5 ϩ cells,

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“…23 The T3 thyroid hormone is a good example of a factor whose developmental effects depend on the expression pattern of its receptors. It promotes OPC specification and proliferation when interacting only with the thyroid hormone receptor (THR) a receptor, 24 but it also plays a role in myelin protein production in mature OLs when both THRa and b are expressed.…”

Section: Defined Stages Of Ol Developmentmentioning

confidence: 99%

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

2008

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Apoptosis plays a crucial role in brain development by ensuring that only appropriately growing, migrating, and synapse-forming neurons and their associated glial cells survive. This process involves an intimate relationship between cell-cell interactions and developmental cues and is further impacted by environmental stress during neurogenesis and disease. Oligodendrocytes (OLs), the major myelin-forming cells in the central nervous system, largely form after this wave of neurogenesis but also show a selective vulnerability to cell death stimuli depending on their stage of development. This can affect not only embryonic and early postnatal brain formation but also the response to demyelinating pathologies. In the present review, we discuss the stagespecific sensitivity of OL lineage cells to damage-induced death and how this might impact myelin survival and regeneration during injury or disease. Apoptosis is a major form of programmed cell death required for the normal development of metazoan tissues, including the brain. 1 During embryonic development of the brain, many more cells than ultimately needed are generated and then selection occurs, resulting in the apoptotic depletion of the surplus cells. The importance of the apoptotic pathway in early brain development has been demonstrated by the targeted deletion in mice of the death-specific cysteine proteases caspase-3 or caspase-9, or of the co-activator Apaf-1, all of which cause severe brain overgrowth and perinatal death. 2,3 In the adult brain, 90% of the cells belong to the glial lineage, which includes oligodendrocytes (OLs), astrocytes and microglia. The glia ensures proper development, function and repair of the neuronal network. This is possible through continuous cross-talk between the glia and neurons mediated by neurotransmitters, cytokines, growth and trophic factor secretion and signaling in a reciprocal manner. [4][5][6][7] In the central nervous system (CNS), OLs are responsible for axon myelination, which insulates the electrical signals transmitted between neurons. OL and neuron development is tightly regulated and the myelin sheath is constructed only when OLs reach maturity and neurons have grown appropriately. In response to injury or during the course of neurological diseases, the neuron-glia network can be replenished to some extent but the degree of repair is dependent on the developmental stage of the OL. This complexity is compounded by the differential sensitivity of OL lineage cells to apoptotic stimuli. In the present review, we will first briefly examine the stages of differentiation of OL cells and then discuss several diseases that are impacted by OL apoptosis, noting how the stage of cell differentiation governs the sensitivity to apoptosis. Defined Stages of OL DevelopmentOligodendrocyte development can be divided into four distinct stages according to the temporal expression of cell surface markers and morphology (Table 1). 8 In the first stage, OL progenitor cells (OPCs) originate from the neuroepithelium of the ventricul...

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Triiodothyronine is a survival factor for developing oligodendrocytes

Cited by 77 publications

References 60 publications

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Distinctive Properties of Human Adult Brain-Derived Myelin Progenitor Cells

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

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