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Eliprodil stimulates CNS myelination

New prospects for multiple sclerosis?

From the Biologie des Interactions Neurones/Glie (Drs. Demerens, Stankoff, Zalc, and Lubetzki), INSERM U-495, Université Pierre et Marie Curie, and the Fédération de Neurologie (Drs. Stankoff and Lubetzki), Hôpital de la Salpêtrière, Paris, France.

Address correspondence and reprint requests to Dr. Catherine Lubetzki, Biologie des Interactions Neurones/Glie, INSERM U-495, Hôpital de la Salpêtrière, 75651, Paris Cedex 13, France.

OBJECTIVE: To examine the potential of eliprodil—a neuroprotective agent with a high affinity for -receptors—to promote myelination in neuron-oligodendrocytes cocultures.

BACKGROUND: Remyelination is one of the major therapeutic issues in MS. Because neuronal integrity is required for CNS myelination, the authors postulated that neuroprotective molecules might favor myelination.

METHODS: Two experimental culture conditions were compared: standard medium Bottenstein and Sato ([B-S] medium) and a medium depleted of both thyroid hormones and progesterone (depleted [D] medium). Myelination was quantified by counting the number of myelinated internodes, identified immunocytochemically with an antimyelin basic protein (anti-MBP) antibody.

RESULTS: The authors first confirmed that in D medium myelination was reduced by a factor of 3.5 compared with cultures maintained in B-S medium. Under both culture conditions, addition of 10^-6 M eliprodil did not modify significantly the total number of either microtubule associated protein-2-positive neurons or MBP-positive oligodendrocytes. However, eliprodil induced a twofold (p < 0.01) increase in myelination when added to B-S medium, and a 4.7-fold (p < 0.0001) increase when added to D medium.

CONCLUSIONS: Although the molecular mechanism mediating the effect of the -receptor agonist on myelination remains to be elucidated, these results strongly suggest that neuroprotective molecules may be of therapeutic interest in demyelinating diseases such as MS.

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