Eliprodil stimulates CNS myelination - New prospects for multiple sclerosis?

Objective: To examine the potential of eliprodil-a neuroprotective agent wi th a high affinity for sigma-receptors-to promote myelination in neuron-oli godendrocytes cocultures. Background: Remyelination is one of the major the rapeutic issues in MS. Because neuronal integrity is required for CNS myeli nation, the authors postulated that neuroprotective molecules might favor m yelination. Methods: Two experimental culture conditions were compared: sta ndard medium Bottenstein and Sate ([B-S] medium) and a medium depleted of b oth thyroid hormones and progesterone (depleted [D] medium). Myelination wa s quantified by counting the number of myelinated internodes, identified im munocytochemically with an antimyelin basic protein(anti-MBP) antibody. Res ults: 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 b oth culture conditions, addition of 10(-6) M eliprodil did not modify signi ficantly the total number of either microtubule associated protein-2-positi ve neurons or MBP-positive oligodendrocytes. However, eliprodil induced a t wofold (p < 0.01) increase in myelination when added do 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 sigma-receptor agonis t an myelination remains to be elucidated, these results strongly suggest t hat neuroprotective molecules may be of therapeutic interest in demyelinati ng diseases such as MS.