Division of Soft Matter Physics, Department of Physics, and Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany.
FASEB J. 2011 Feb;25(2):624-31. doi: 10.1096/fj.10-163790. Epub 2010 Oct 25.
Increased stiffness of reactive glial cells may impede neurite growth and contribute to the poor regenerative capabilities of the mammalian central nervous system. We induced reactive gliosis in rodent retina by ischemia-reperfusion and assessed intermediate filament (IF) expression and the viscoelastic properties of dissociated single glial cells in wild-type mice, mice lacking glial fibrillary acidic protein and vimentin (GFAP(-/-)Vim(-/-)) in which glial cells are consequently devoid of IFs, and normal Long-Evans rats. In response to ischemia-reperfusion, glial cells stiffened significantly in wild-type mice and rats but were unchanged in GFAP(-/-)Vim(-/-) mice. Cell stiffness (elastic modulus) correlated with the density of IFs. These results support the hypothesis that rigid glial scars impair nerve regeneration and that IFs are important determinants of cellular viscoelasticity in reactive glia. Thus, therapeutic suppression of IF up-regulation in reactive glial cells may facilitate neuroregeneration.
反应性神经胶质细胞硬度增加可能会阻碍神经突生长,并导致哺乳动物中枢神经系统再生能力差。我们通过缺血再灌注诱导啮齿动物视网膜发生反应性神经胶质增生,并在野生型小鼠、缺乏胶质纤维酸性蛋白和波形蛋白的小鼠(GFAP(-/-)Vim(-/-))以及正常的 Long-Evans 大鼠中评估中间丝 (IF) 的表达和分离的单个神经胶质细胞的粘弹性特性。在缺血再灌注反应中,野生型小鼠和大鼠的神经胶质细胞显著变硬,但 GFAP(-/-)Vim(-/-)小鼠的神经胶质细胞没有变化。细胞硬度(弹性模量)与 IF 的密度相关。这些结果支持这样的假设,即坚硬的神经胶质瘢痕会损害神经再生,而 IF 是反应性神经胶质细胞粘弹性的重要决定因素。因此,抑制反应性神经胶质细胞中 IF 的上调可能有助于神经再生。