Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis?
Multiple sclerosis is affecting approximately 1 out of every 1000 individuals in the western world. After axons are denuded of myelin in the early stages of the disease, remyelination occurs, but eventually this process fails, and permanent disability is the result. During development, the polysialylated form of the neural cell adhesion molecule NCAM, PSA-NCAM, is expressed at the axonal surface and acts as a negative regulator of myelination, presumably by preventing myelin-forming cells from attaching to the axon. Removal of PSA-NCAM from the axonal surface is a prerequisite for the initiation of myelination. We questioned whether, in multiple sclerosis, re-expression of PSA-NCAM by axons could occur, and therefore account for the failure of remyelination. Forty multiple sclerosis lesions from 24 different post-mortem multiple sclerosis cases were selected by histological methods and analysed by immunohistochemistry. Demyelinated lesions and partially remyelinated lesions (shadow plaques) were studied. Controls consisted of post-mortem brain tissue from patients with amyotrophic lateral sclerosis and without neurological disease. We showed that PSA-NCAM, normally absent from adult brain, is re-expressed on demyelinated axons in the plaques. Within shadow plaques, remyelinated axons do not express PSA-NCAM. Re-expression of PSA-NCAM could act as an inhibitor of remyelination and participate in disease progression in multiple sclerosis.
Charles
Perrine
P
Biologie des Interactions Neurones/Glie, INSERM U495, UPMC, Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 75651 Paris cedex 13, France.
Reynolds
Richard
R
Seilhean
Danielle
D
Rougon
Geneviève
G
Aigrot
Marie S
MS
Niezgoda
Adam
A
Zalc
Bernard
B
Lubetzki
Catherine
C
D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D006801:Humans; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D009186:Myelin Sheath / Q000187:drug effects*; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*
D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule