title: Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis.
abstract: To compare effects of insulin-like growth factor I (IGF-I) and placebo treatment on lesions that resemble those seen during active demyelination in multiple sclerosis, we induced experimental autoimmune encephalomyelitis in Lewis rats with an emulsion containing guinea pig spinal cord and Freund's adjuvant. On day 12-13, pairs of rats with the same degree of weakness were given either IGF-I or placebo intravenously twice daily for 8 days. After 8 days of placebo or IGF-I (200 micrograms/day or 1 mg/day) treatment, the spinal cord lesions were studied by in situ hybridization and with immunocytochemical and morphological methods. IGF-I produced significant reductions in numbers and areas of demyelinating lesions. These lesions contained axons surrounded by regenerating myelin segments instead of demyelinated axons seen in the placebo-treated rats. Relative mRNA levels for myelin basic protein, proteolipid protein (PLP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase in lesions of IGF-I-treated rats were significantly higher than they were in placebo-treated rats. PLP mRNA-containing oligodendroglia also were more numerous and relative PLP mRNA levels per oligodendrocyte were higher in lesions of IGF-I-treated rats. Finally, a significantly higher proportion of proliferating cells were oligodendroglia-like cells in lesions of IGF-I-treated rats. We think that IGF-I effects on oligodendrocytes, myelin protein synthesis, and myelin regeneration reduced lesion severity and promoted clinical recovery in this experimental autoimmune encephalomyelitis model. These IGF-I actions may also benefit patients with multiple sclerosis.
authors.affiliation: Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Yao
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: L D
authors.initials: LD
authors.lastname: Hudson
authors.forename: H D
authors.initials: HD
authors.lastname: Webster
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000096:biosynthesis; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009185:Myelin Proteins / Q000032:analysis / Q000096:biosynthesis*; D018991:Myelin Proteolipid Protein; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014168:Transferrin / Q000032:analysis
chemical_list: D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D014168:Transferrin; D007334:Insulin-Like Growth Factor I; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases