日本薬理学会年会要旨集
Online ISSN : 2435-4953
WCP2018 (The 18th World Congress of Basic and Clinical Pharmacology)
セッションID: WCP2018_PO4-1-73
会議情報

Poster session
Can remyelination be enhanced by immunomodulatory therapeutic modality?
Rina AharoniMichael SelaRuth Arnon
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会議録・要旨集 オープンアクセス

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抄録

An essential challenge for multiple sclerosis (MS) therapy is not only to ameliorate the inflammatory aspect of the disease, but to promote repair and remyelination. Glatiramer acetate (GA, Copaxone), an approved MS treatment, has been shown to induce immunomodulation and neuroprotection in MS and in its animal model experimental autoimmune encephalomyelitis (EAE).

The effect of GA on remyelination was studied in both relapsing-remitting and chronic EAE, using electron microscopy and immunohistochemistry. Reduced myelin damages were detected, even when GA-treatment was applied after the disease exacerbation, suggesting repair. Moreover, quantitative transmission electron microscopy (TEM) revealed significant elevation in remyelinated axons as well as in the ratio of remyelinated to demyelinated axons in GA-treated compared to untreated EAE-mice. This pattern was also evident by MRI using magnetization transfer ratio (MTR), which indicates myelin loss. Overall assessment of the whole brain by histogram analysis as well as detection of specific affected areas by voxel-based analysis revealed restoration of the MTR values to the normal level following GA treatment.

To test if GA can indeed promote myelination, we studied its effect in the developing CNS, when injected postnatally to newborn mice. Immunohistochemical and ultrastructural analyses indicated increase in myelinated axons, and the thickness of the myelin encircling them, in spinal cords of GA-injected mice compared to their PBS-injected littermates.

We further developed a novel quantitative strategy to in situ label and visualize newly synthesized myelin using metabolic incorporation of the choline analog propargyl-choline (P-Cho) into the CNS. Colocalization analysis of myelin metabolic labeling confirmed more remyelination in GA-treated mice compared to untreated EAE-mice, as indicated by both the area and the intensity of P-Cho incorporation specifically into the myelin.

A prominent elevation in progenitor oligodendrocytes and their proliferation as well as in mature oligodendrocytes indicated that the effect of GA is linked to increased proliferation and differentiation along the oligodendroglial cascade. In addition, increased in situ expression of neurotrophic factors suggests that the mode of action of GA in this system can be attributed to neurotrophic effect. These cumulating findings support the notion that repair process in the CNS can be up-regulated by therapy.

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© 2018 The Authors(s)
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