Tansey F A, Zhang H, Cammer W
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Neurochem Res. 1996 Apr;21(4):411-6. doi: 10.1007/BF02527704.
The aim of this study was to identify events that might take place in oligodendrocytes early in the process of demyelination, i.e., before the occurrence of massive loss of myelin. It was considered important to focus on demyelination and remyelination in young adults, in whose brains there would be relatively few juvenile glial precursor cells. CAII mRNA and protein were used to monitor changes in oligodendrocytes during cuprizone intoxication in the mice. After four or eight weeks of cuprizone feeding CAII message became less plentiful in oligodendrocyte processes. Two days after removal of cuprizone CAII message had appeared in those cell processes. Four or eight weeks after beginning cuprizone feeding CAII protein had decreased approximately 25% in forebrain homogenates. The loss of CAII protein was reversible after four weeks on cuprizone, but not after eight weeks. After four weeks of cuprizone feeding the numbers of CAII mRNA-positive oligodendrocytes had decreased by approximately 50%, and after eight weeks, by approximately 80%. By 12 weeks, however, the number of oligodendrocytes expressing CAII mRNA had spontaneously returned to normal levels. Before eight weeks of cuprizone feeding, loss of myelinated tracts in the corpus striatum was reversible. Demyelination appeared to become irreversible after nine weeks of intoxication, although expression of CAII mRNA remained reversible. The results suggest that in the brain of the young adult, oligodendrocytes expressing message for CAII can be generated spontaneously shortly before demyelination becomes irreversible, and can survive and continue to express CAII mRNA but not CAII protein.
本研究的目的是确定在脱髓鞘过程早期，即髓鞘大量丢失之前，少突胶质细胞可能发生的事件。研究认为，关注年轻成年人的脱髓鞘和髓鞘再生很重要，因为在他们的大脑中，幼年神经胶质前体细胞相对较少。利用碳酸酐酶II（CAII）的信使核糖核酸（mRNA）和蛋白质来监测小鼠在食用双环己酮草酰二腙（cuprizone）中毒期间少突胶质细胞的变化。在喂食双环己酮草酰二腙四周或八周后，CAII信使在少突胶质细胞突起中变得不那么丰富。去除双环己酮草酰二腙两天后，CAII信使出现在那些细胞突起中。在开始喂食双环己酮草酰二腙四周或八周后，前脑匀浆中的CAII蛋白质减少了约25%。在食用双环己酮草酰二腙四周后，CAII蛋白质的损失是可逆的，但八周后则不可逆。在喂食双环己酮草酰二腙四周后，CAII mRNA阳性少突胶质细胞的数量减少了约50%，八周后减少了约80%。然而，到12周时，表达CAII mRNA的少突胶质细胞数量已自发恢复到正常水平。在喂食双环己酮草酰二腙八周之前，纹状体中髓鞘束的丢失是可逆的。在中毒九周后，脱髓鞘似乎变得不可逆，尽管CAII mRNA的表达仍然是可逆的。结果表明，在年轻成年人的大脑中，表达CAII信使的少突胶质细胞可以在脱髓鞘变得不可逆之前不久自发产生，并且可以存活并继续表达CAII mRNA，但不表达CAII蛋白质。
