Delayed Changes in Growth Factor Gene Expression during Slow Remyelination in the CNS of Aged Rats

Hinks, G.L.; Franklin, Robin J.M.

doi:10.1006/mcne.2000.0897

Cited by 149 publications

(107 citation statements)

References 57 publications

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“…The decrease in CNS remyelination rates occurring as a consequence of aging is a major complication for remyelinating therapies, in particular for long-lasting demyelinating disorders such as MS. It is also important to consider the age-related modifications of the innate immune and growth factor responses to the demyelination process which interfere with myelin repair (Hinks and Franklin 2000;Zhao et al 2006). Studies of OPC response during remyelination of toxin-induced demyelination in the caudal cerebellar peduncle from young and old adult rats indicate that the inefficiency of remyelination associated with aging is due to the impairment of OPC recruitment and the subsequent failure of OPCs in differentiating into myelinating OL (Sim et al 2002).…”

Section: Remyelination and Agingmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits. This process is often deficient in demyelinating diseases such as multiple sclerosis (MS), and the reasons for the failure of repair mechanisms remain unclear. The characterization of these mechanisms and the factors involved in the proliferation, recruitment, and differentiation of oligodendroglial progenitor cells is key in designing strategies to improve remyelination in demyelinating disorders. First, a very dynamic combination of different molecules such as growth factors, cytokines, chemokines, and different signaling pathways is tightly regulated during the remyelination process. Second, factors unrelated to this pathology, i.e., age and genetic background, may impact disease progression either positively or negatively, and in particular, age-related remyelination failure has been proven to involve oligodendroglial cells aging and their intrinsic capacities among other factors. Third, nutrients may either help or hinder disease progression. Experimental evidence supports the anti-inflammatory role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive inhibition of arachidonic acid, whose metabolites participate in inflammation, and the reduction in T cell proliferation. In turn, vitamin D intake and synthesis have been associated with lower MS incidence levels, while vitamin D-gene interactions might be involved in the pathogenesis of MS. Finally, dietary polyphenols have been reported to mitigate demyelination by modulating the immune response.

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Section: Remyelination and Agingmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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“…The loss of neural precursor capacity to respond to demyelination signals could result from changes with aging in interactions between growth factors and their receptors. Indeed, LPC-induced demyelination in the spinal cord induces a delayed and lower peak expression in platelet-derived growth factor (PDGF), IGF-1, and TGF-␤1 in aged rats compared with young ones, which is correlated with a decreased potential for remyelination (Hinks and Franklin, 2000).…”

Section: Consequences Of Age On the Capacity Of Neural Precursors To mentioning

confidence: 99%

“…This failure is reproduced in animal models; remyelination after lysolecithin (LPC)-induced demyelination remains incomplete in the CNS of old rats (Gilson and Blakemore, 1993). This failure in remyelination results most likely from a decrease in the speed of remyelination (Shields et al, 1999) and seems to be correlated with modifications of growth factor expression (Hinks and Franklin, 2000). We previously showed that LPC-induced demyelination of the adult corpus callosum also activates neural precursors from the SVZ, promoting their proliferation, mobilization in the lesioned corpus callosum, and differentiation into astrocytes and oligodendrocytes (Nait-Oumesmar et al, 1999;.…”

mentioning

confidence: 98%

Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination

Decker

Picard-Riéra

Lachapelle

et al. 2002

J of Neuroscience Research

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Precursor cells of the adult mouse subventricular zone (SVZ) are mobilized and recruited by a lysolecithin (LPC)-induced demyelination of the corpus callosum. Because age decreases the proliferation of the SVZ neural precursors as well as the potential for myelin repair of the adult central nervous system, we have compared the ability of young and aged adult neural precursors to respond to LPC-induced demyelination. With age, the SVZ cells lost their capacity to proliferate and to be recruited by the lesion. Whereas a single injection of fibroblast growth factor-2 or transforming growth factor-␣ stimulated the proliferation of SVZ and rostral migratory stream precursors in both groups of animals after demyelination, they favored recruitment at the lesion in young mice but not in aged ones. In vitro experiments using neurospheres derived from young and aged animals indicated that both populations have the same migratory performances. Our in vivo data thus suggest that aged neural precursors may loose their intrinsic capacities to respond to demyelination-induced signals. Alternatively, their function may be altered by modification of the aged extracellular environment.

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“…Besides previous investigations on glial growth factors, 18,19 recent studies have suggested the re-expression of developmentally regulated oligodendroglial pathways or cytoskeletal proteins during remyelination. 20 -22 It is therefore tempting to investigate the role of additional Supported by the Gemeinnü tzige Hertie-Stiftung, the Max Planck Society, and the Deutsche Forschungsgemeinschaft (through SFB 406).…”

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confidence: 95%

Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination

Herrero-Herranz¹,

Pardo²,

Bunt³

et al. 2007

The American Journal of Pathology

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Mechanisms of lesion repair in multiple sclerosis are incompletely understood. To some degree, remyelination can occur, associated with an increase of proliferating oligodendroglial cells. Recently, the expression of potassium channels has been implicated in the control of oligodendrocyte precursor cell proliferation in vitro. We investigated the expression of Kv1.4 potassium channels in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Confocal microscopy revealed expression of Kv1.4 in AN2-positive oligodendrocyte precursor cells and premyelinating oligodendrocytes in vitro but neither in mature oligodendrocytes nor in the spinal cords of healthy adult mice. After induction of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, Kv1.4 immunoreactivity was detected in or around lesions already during disease onset with a peak early and a subsequent decrease in the late phase of the disease. Kv1.4 expression was confined to 2,3-cyclic nucleotide 3-phosphodiesterase-positive oligodendroglial cells, which were actively proliferating and ensheathed naked axons. After a demyelinating episode, the number of Kv1.4 and 2,3-cyclic nucleotide 3-phosphodiesterase double-positive cells was greatly reduced in ciliary neurotrophic factor knockout mice, a model with impaired lesion repair. In summary, the re-expression of an oligodendroglial potassium channel may have a functional implication on oligodendroglial cell cycle progression, thus influencing tissue repair in experimental autoimmune encephalomyelitis and multiple sclerosis.

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Delayed Changes in Growth Factor Gene Expression during Slow Remyelination in the CNS of Aged Rats

Cited by 149 publications

References 57 publications

Nutritional factors and aging in demyelinating diseases

Nutritional factors and aging in demyelinating diseases

Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination

Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination

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