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PMID: 1371885 Published · ppublish English Journal Article

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 5 ·1992-03-01 ·Pages 1894-8

Komoly S, Hudson LD, Webster HD, Bondy CA

Abstract

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.

MeSH Terms
2',3'-Cyclic-Nucleotide Phosphodiesterases/metabolism Animals Astrocytes/physiology Cuprizone/pharmacology Demyelinating Diseases/chemically induced,genetics Gene Expression Glial Fibrillary Acidic Protein/metabolism Immunoenzyme Techniques Insulin-Like Growth Factor I/genetics Male Mice Myelin Basic Protein/metabolism Nerve Tissue Proteins/metabolism Nucleic Acid Hybridization Proteolipids/metabolism RNA, Messenger/genetics Receptors, Cell Surface/genetics,metabolism Receptors, Somatomedin
Chemicals
Glial Fibrillary Acidic Protein Myelin Basic Protein Nerve Tissue Proteins Proteolipids RNA, Messenger Receptors, Cell Surface Receptors, Somatomedin Cuprizone Insulin-Like Growth Factor I 2',3'-Cyclic-Nucleotide Phosphodiesterases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Komoly S
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Hudson L D
Webster H D
Bondy C A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.5.1894
Published
1992-03-01
Pages
1894-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48560
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.89.5.1894 PMC Full Text View journal details
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