Komoly S, Hudson L D, Webster H D, Bondy C A
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1894-8. doi: 10.1073/pnas.89.5.1894.
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.
为了研究实验性脱髓鞘和髓鞘再生过程中胰岛素样生长因子I（IGF-I）及IGF-I受体基因的表达情况，给幼鼠喂食双环己酮草酰二腙（cuprizone）。这种铜螯合剂可导致胼胝体和上小脑脚发生脱髓鞘，停止治疗后则会迅速发生髓鞘再生。在cuprizone治疗及恢复过程中的不同时间点，取脑切片与特异性探针杂交，并用抗体进行免疫染色，以确定IGF-I和IGF-I受体mRNA及肽段的定位和相对含量。在未处理的同窝幼鼠中，白质中未检测到IGF-I和IGF-I受体mRNA及肽段。在cuprizone处理的小鼠中，髓鞘破坏区域的星形胶质细胞表达高水平的IGF-I mRNA和肽段。恢复过程中星形胶质细胞的IGF-I表达迅速下降，而少突胶质细胞中髓鞘相关基因的表达增加。在严重脱髓鞘区域，未成熟的少突胶质细胞在恢复早期IGF-I受体mRNA和肽段免疫反应性出现短暂增加。脱髓鞘过程中星形胶质细胞中IGF-I诱导的这种高度特异性模式以及恢复过程中再生少突胶质细胞中IGF-I受体的表达表明，IGF-I在体内少突胶质细胞和髓鞘代谢的调节中发挥作用。
