Insulin-like growth factor I increases myelination and inhibits demyelination in cultured organotypic nerve tissue.
The implication of insulin-like growth factor I (IGF-I) in the myelination and the repair of myelin that occur after a demyelinating process was evaluated in organotypic cultures of embryonic nerve tissue. The amount of myelin of mouse spinal cord explants exposed to media supplemented with IGF-I beginning on the first day of explantation was recorded by light-microscopic examination and quantitation of the 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity. After 9 days in vitro (DIV), the cultures treated with medium supplemented with 0.1-1 microgram/ml IGF-I showed a greater amount of myelin and an increase over the controls in CNPase activity between 50 and 80% at 16 DIV and 100% at 21 DIV. Total demyelination with a concomitant reduction of about 80% in the CNPase activity resulted when anti-white matter antiserum and complement were added to the nutrient medium of fully myelinated cultures. This effect was partially reverted when IGF-I was included in the demyelinating medium. The higher inhibition, about 50%, was obtained with concentrations of IGF-I between 0.1 and 0.5 micrograms/ml. To study the effect of IGF-I on remyelination, well-myelinated cultures were completely demyelinated, maintained in that state for 2 or 15 DIV and after that allowed to remyelinate for 14 days. Cultures exposed to medium supplemented with 0.01-0.1 microgram/ml IGF-I showed a degree of remyelination similar to that of the normal nutrient medium-fed cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D003711:Demyelinating Diseases / Q000378:metabolism / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009417:Nerve Tissue / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases