Ludwin S K
Department of Pathology, University of Western Ontario, London, Canada.
Acta Neuropathol. 1992;84(5):530-7. doi: 10.1007/BF00304472.
It has previously been shown in the adult rat optic nerve that cells with many features of oligodendrocytes are capable of surviving for extended periods of time in the absence of axons. This is in contrast to the situation in the developing nervous system, where removal of axons leads to the failure of differentiation and to the death of oligodendrocytes. In the adult, these surviving oligodendrocytes were not typical in their appearance, and could only be identified with certainty using cell specific markers. In the present experiments, the functional capacity of these long-term quiescent cells to regenerate and myelinate was tested using the Shiverer mouse, a mutant lacking the gene for myelin basic protein (MBP), as a host animal. Fragments of optic nerve from adult rats which had been enucleated up to 2 years previously, were implanted into neonatal Shiverer mice. Four weeks later, the brains were removed and the formation of myelin investigated with antibodies to MBP, to ensure that this was of donor origin. Axons were demonstrated to have grown into the implants, and may have provided the stimulus for the production of MBP by the oligodendrocytes, which were stained positively within the implant. Myelin was demonstrated both within and adjacent to the implant. This study indicates that in the adult central nervous system, cells can survive for extended periods of time in the absence of axons, albeit in an inactive state, and are then capable of functional regeneration when placed in contact with unmyelinated axons. The origin of these cells, either from surviving oligodendrocytes which had previously myelinated the axons, or from progenitors lying within the adult nerve is unclear. The implications of these results are of importance in the further investigation of the potential for central nervous system regeneration.
先前在成年大鼠视神经中已表明,具有许多少突胶质细胞特征的细胞在没有轴突的情况下能够长时间存活。这与发育中的神经系统的情况形成对比,在发育中的神经系统中,轴突的去除会导致少突胶质细胞分化失败和死亡。在成年动物中,这些存活的少突胶质细胞外观并不典型,只有使用细胞特异性标记物才能确切识别。在本实验中,使用颤抖小鼠(一种缺乏髓鞘碱性蛋白(MBP)基因的突变体)作为宿主动物,测试了这些长期静止细胞再生和髓鞘形成的功能能力。将成年大鼠在长达2年前摘除眼球后的视神经片段植入新生颤抖小鼠体内。四周后,取出大脑,用抗MBP抗体研究髓鞘形成情况,以确保其来源于供体。已证明轴突已长入植入物中,并且可能为少突胶质细胞产生MBP提供了刺激,少突胶质细胞在植入物中呈阳性染色。在植入物内部和附近均发现了髓鞘。这项研究表明,在成年中枢神经系统中,细胞在没有轴突的情况下能够长时间存活,尽管处于非活动状态,并且当与无髓鞘轴突接触时能够进行功能再生。这些细胞的起源,要么来自先前已为轴突形成髓鞘的存活少突胶质细胞,要么来自成年神经内的祖细胞,目前尚不清楚。这些结果的意义对于进一步研究中枢神经系统再生的潜力具有重要意义。