Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination.
To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression during experimental demyelination and myelin regeneration, young mice were fed cuprizone (( bis(cyclohexanone) oxaldihydrazone )). This copper-chelating agent produces demyelination in the corpus callosum and superior cerebellar peduncles, and when treatment is stopped, there is rapid remyelination. At intervals during cuprizone treatment and recovery, brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF-I and IGF-I receptor mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and peptides were not detected in white matter. In cuprizone-treated mice, high levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery and oligodendroglial expression of myelin-related genes increased. In severely demyelinated areas, immature oligodendroglia exhibited a transient increase in IGF-I receptor mRNA and peptide immunoreactivity during early recovery. This highly specific pattern of IGF-I induction in astrocytes during demyelination and the expression of the IGF-I receptor in regenerating oligodendrocytes during recovery suggest that IGF-I functions in the regulation of oligodendrocyte and myelin metabolism in vivo.
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
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S
Komoly
L D
LD
Hudson
H D
HD
Webster
C A
CA
Bondy
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics*; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D011510:Proteolipids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D017451:Receptors, Somatomedin
D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D011510:Proteolipids; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D003471:Cuprizone; D007334:Insulin-Like Growth Factor I; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases