Eliprodil stimulates CNS myelination
New prospects for multiple sclerosis?
- Corinne Demerens, PhD,
- Bruno Stankoff, MD,
- Bernard Zalc, MD, PhD and
- Catherine Lubetzki, MD, PhD
- From the Biologie des Interactions Neurones/Glie (Drs. DemerensStankoff, 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.
Abstract
Objective: To examine the potential of eliprodil—a neuroprotective agent with a high affinity for ς-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 ς-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.
- Received May 11, 1998.
- Accepted October 10, 1998.
