Baracskay Karen L, Duchala Cynthia S, Miller Robert H, Macklin Wendy B, Trapp Bruce D
Department of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
J Neurosci Res. 2002 Dec 1;70(5):645-54. doi: 10.1002/jnr.10418.
The factors that regulate oligodendrogenesis have been studied extensively in optic nerve, where oligodendrocyte production and myelination quickly follow colonization of the nerve by progenitor cells. In contrast, oligodendrocyte production in the cerebral cortex begins approximately 1 week after progenitor cell colonization and continues for 3-4 weeks. This and other observations raise the possibility that oligodendrogenesis is regulated by different mechanisms in white and gray matter. The present study examined oligodendrocyte production in the developing cerebral cortex of jimpy (jp) and jimpy(msd) (msd) mice, which exhibit hypomyelination and oligodendrocyte death due to mutations in and toxic accumulations of proteolipid protein, the major structural protein of CNS myelin. Proliferation of oligodendrocyte progenitors and production of myelinating oligodendrocytes was reduced in jp cerebral cortex when compared to wild-type (wt) and msd mice. The incidence of oligodendrocyte cell death was similar in jp and msd cortex, but total dying oligodendrocytes were greater in msd. We confirm previous reports of increased oligodendrocyte production in white matter of both jp and msd mice. The jp mutation, therefore, reduces oligodendrocyte production in cerebral cortex but not in white matter. These data provide additional evidence that oligodendrogenesis is differentially regulated in white matter and gray matter and implicate PLP/DM20 as a modulator of these differences.
调节少突胶质细胞生成的因素已在视神经中得到广泛研究，在视神经中，祖细胞定殖后，少突胶质细胞的产生和髓鞘形成很快就会发生。相比之下，大脑皮质中少突胶质细胞的产生在祖细胞定殖后约1周开始，并持续3 - 4周。这一现象以及其他观察结果提示，少突胶质细胞生成在白质和灰质中可能受不同机制调控。本研究检测了jimpy（jp）和jimpy(msd)（msd）小鼠发育中的大脑皮质中的少突胶质细胞生成情况，这两种小鼠由于中枢神经系统髓鞘的主要结构蛋白蛋白脂质蛋白的突变和毒性积累而表现出髓鞘形成减少和少突胶质细胞死亡。与野生型（wt）和msd小鼠相比，jp大脑皮质中少突胶质细胞祖细胞的增殖和有髓鞘形成的少突胶质细胞的产生减少。jp和msd皮质中少突胶质细胞死亡的发生率相似，但msd中总的死亡少突胶质细胞更多。我们证实了之前关于jp和msd小鼠白质中少突胶质细胞生成增加的报道。因此，jp突变减少了大脑皮质而非白质中的少突胶质细胞生成。这些数据提供了额外的证据，表明少突胶质细胞生成在白质和灰质中受到不同的调节，并表明PLP/DM20是这些差异的调节因子。
