Expression of insulin-like growth factors in remyelination following ethidium bromide-induced demyelination in the mouse spinal cord.

Abstract

Insulin-like growth factors, IGF-I and IGF-II, play important roles in development and myelination in the CNS, but little is known about the response of IGF after demyelination. The present study investigated the expression of IGF and their cognitive receptors in the process of remyelination following ethidium bromide (EBr)-induced demyelination in the adult mouse spinal cord. The present results, in a quantitative real-time PCR, showed significant increases in the levels of the mRNA for both IGF-I and IGF-II during both the demyelination and remyelination stages. The levels of IGF-I receptor (IGF-IR) mRNA increased from 10 days to 4 weeks after the EBr injection. The levels of IGF-II receptor (IGF-IIR) mRNA decreased for 6 days and then increased 10 days after the EBr injection. In situ hybridization studies showed the cells expressing IGF-I mRNA to be mainly macrophage-like cells, while those expressing IGF-II mRNA were predominantly Schwann cell-like cells invading the demyelinating lesion. The immunoreactivity for the IGF-IR and IGF-IIR increased in various kinds of cells within and around the demyelinating lesions from 6 days to 4 weeks after the EBr injection. These results suggest that locally produced IGF could partly be involved in some mechanisms underlying remyelination processes following the EBr-induced demyelination in the mouse spinal cord.