Nakatsuji Y, Miller R H
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Glia. 1998 Apr;22(4):379-89. doi: 10.1002/(sici)1098-1136(199804)22:4<379::aid-glia7>3.0.co;2-z.
The normal adult vertebrate nervous system is a relative quiescent tissue in terms of cell proliferation. However, astrocytes in many regions of the central nervous system (CNS) retain the capacity to undergo cell division. To examine the mechanisms that regulate the proliferation of astrocytes in the CNS we have utilized an in vitro assay in which astrocyte density and cellular environment could be regulated. We demonstrate that type 1 astrocytes derived from the cerebral cortex of developing rats exhibit a profound density-dependent inhibition of proliferation. This inhibition of proliferation was cell type specific, but not restricted to type 1 astrocytes. NIH 3T3 cells but not smooth muscle cells inhibited astrocyte proliferation, while contact-inhibited astrocytes did not inhibit oligodendrocyte proliferation. Co-culture of type 1 astrocytes with neurons from a variety of sources resulted in induction of a process-bearing astrocyte morphology and promoted glial cell proliferation. Thus, induction of a process-bearing astrocyte morphology does not lead to a cessation of proliferation. The inhibition of astrocyte proliferation did not appear to be mediated through the release or sequestration of soluble factors but rather could be induced by membrane-associated factors.
就细胞增殖而言,正常成年脊椎动物的神经系统是一种相对静止的组织。然而,中枢神经系统(CNS)许多区域的星形胶质细胞保留了进行细胞分裂的能力。为了研究调节中枢神经系统中星形胶质细胞增殖的机制,我们利用了一种体外试验,在该试验中可以调节星形胶质细胞密度和细胞环境。我们证明,源自发育中大鼠大脑皮层的1型星形胶质细胞表现出对增殖的显著密度依赖性抑制。这种增殖抑制是细胞类型特异性的,但不限于1型星形胶质细胞。NIH 3T3细胞而非平滑肌细胞抑制星形胶质细胞增殖,而接触抑制的星形胶质细胞不抑制少突胶质细胞增殖。将1型星形胶质细胞与来自多种来源的神经元共培养,导致具有突起的星形胶质细胞形态的诱导并促进神经胶质细胞增殖。因此,具有突起的星形胶质细胞形态的诱导不会导致增殖停止。星形胶质细胞增殖的抑制似乎不是通过可溶性因子的释放或隔离介导的,而是可以由膜相关因子诱导的。