Morell P, Barrett C V, Mason J L, Toews A D, Hostettler J D, Knapp G W, Matsushima G K
Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina, 27599-7250, USA.
Mol Cell Neurosci. 1998 Nov;12(4-5):220-7. doi: 10.1006/mcne.1998.0715.
When C57BL/6J mice, 8 weeks of age, received 0.2% Cuprizone in their diet, extensive demyelination in corpus callosum was detectable after 3 weeks, and there was massive demyelination by 4 weeks. As expected, the accumulation of phagocytically active microglia/macrophages correlated closely with demyelination. When Cuprizone was removed from the diet, remyelination was soon initiated; after 6 weeks of recovery, myelin levels were near-normal and phagocytic cells were no longer prominent. Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks. Unexpectedly, upregulation of mRNA for these myelin genes did not correlate with initiation of remyelination but rather with accumulation of microglia/macrophages. After 6 weeks of exposure to Cuprizone, mRNA levels were at control levels or higher-in the face of massive demyelination. This suggests that in addition to effecting myelin removal, microglia/macrophages may simultaneously push surviving oligodendroglia or their progenitors toward myelination.
8周龄的C57BL/6J小鼠在其饮食中摄入0.2%的铜螯合剂后，3周时可检测到胼胝体广泛脱髓鞘，4周时出现大量脱髓鞘。正如预期的那样，具有吞噬活性的小胶质细胞/巨噬细胞的积累与脱髓鞘密切相关。当从饮食中去除铜螯合剂后，髓鞘再生很快开始；恢复6周后，髓鞘水平接近正常，吞噬细胞不再突出。接触铜螯合剂1周后，髓鞘相关糖蛋白、髓鞘碱性蛋白和神经酰胺半乳糖基转移酶的mRNA稳态水平已经显著降低，2周后仅为对照值的10%-20%。出乎意料的是，这些髓鞘基因的mRNA上调与髓鞘再生的开始无关，而是与小胶质细胞/巨噬细胞的积累有关。接触铜螯合剂6周后，尽管存在大量脱髓鞘，mRNA水平仍处于对照水平或更高。这表明，除了影响髓鞘清除外，小胶质细胞/巨噬细胞可能同时促使存活的少突胶质细胞或其祖细胞进行髓鞘形成。
