C Demerens1, B Stankoff, B Zalc, C Lubetzki. 1. Biologie des Interactions Neurones/Glie, INSERM U-495, Université Pierre et Marie Curie, Paris, France.
Abstract
OBJECTIVE: To examine the potential of eliprodil-a neuroprotective agent with a high affinity for sigma-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. CONCLUSION: Although the molecular mechanism mediating the effect of the sigma-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.
OBJECTIVE: To examine the potential of eliprodil-a neuroprotective agent with a high affinity for sigma-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. CONCLUSION: Although the molecular mechanism mediating the effect of the sigma-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.
Authors: S Liu; Y Qu; T J Stewart; M J Howard; S Chakrabortty; T F Holekamp; J W McDonald Journal: Proc Natl Acad Sci U S A Date: 2000-05-23 Impact factor: 11.205
Authors: B Oxombre; C Lee-Chang; A Duhamel; M Toussaint; M Giroux; M Donnier-Maréchal; P Carato; D Lefranc; H Zéphir; L Prin; P Melnyk; P Vermersch Journal: Br J Pharmacol Date: 2015-02-10 Impact factor: 8.739