IGF binding protein alterations on periplaque oligodendrocytes in multiple sclerosis: implications for remyelination.
Why myelin repair greatly fails in multiple sclerosis (MS) is unclear. The insulin-like growth factor (IGF) system plays vital roles in oligodendrocyte development, survival, and myelin synthesis. We used immunohistochemistry to study IGF-I, IGF-I receptors and IGF binding proteins (IGFBPs) 1-6 on oligodendrocytes at the edges of chronic demyelinated plaques and normal appearing white matter of MS, and in cerebral white matter of controls without neurological disease. Oligodendrocytes in all conditions were immunoreactive for IGF-I, IGF-I receptors and IGFBPs-1-5. Oligodendrocytes at the edges of demyelinated plaques displayed enhanced immunoreactivity for IGF-I, IGF-I receptors, IGFBPs-1 and -6. Because increased expression of IGFBPs-1 and -6 has been associated with impaired synthesis of myelin proteins in oligodendrocyte lineage cells, pharmacological approaches to reduce their expression might be useful for promoting remyelination of axons in MS lesions.
Wilczak
Nadine
N
Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands.
Chesik
Daniel
D
Hoekstra
Dick
D
De Keyser
Jacques
J
D000368:Aged; D000369:Aged, 80 and over; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D018970:Insulin-Like Growth Factor Binding Protein 1; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D017526:Receptor, IGF Type 1