Levison S W, Hudgins S N, Crawford J L
Department of Neuroscience and Anatomy, H109, Pennsylvania State University, College of Medicine, P.O. Box 850, Hershey, PA 17033, USA.
Brain Res. 1998 Aug 24;803(1-2):189-93. doi: 10.1016/s0006-8993(98)00594-0.
Studies using transgenic mice that overexpress ciliary neurotrophic factor (CNTF), direct injection of CNTF into brain parenchyma, and ectopic expression of CNTF by an adenoviral vector have demonstrated that CNTF activates astrocytes. Paradoxically, studies to date have failed to show an effect of CNTF on the expression of GFAP by cultured astrocytes. Therefore, the goal of this study was to use nuclear hypertrophy and GFAP expression as indices of glial activation to compare the responsiveness of forebrain type 1 and type 2 astrocytes to CNTF. As reported by others, CNTF did not increase GFAP in type 1 astrocytes; however, it rapidly increased their nuclear size by 20%. Nuclear hypertrophy was apparent within 4 h after CNTF exposure and persisted for at least 48 h. In contrast, type 2 astrocyte GFAP increased 2-fold over the course of 48 h of CNTF treatment. During this same treatment period type 2 astroglial nuclei enlarged by 25%. We conclude that CNTF stimulates both type 1 and type 2 astrocytes directly. Together with our in vivo studies (Levison et al., 1996: Exp. Neurol. 141: 256), these data support the concept that CNTF is responsible for many of the progressive astroglial changes that appear after CNS injury and disease.
利用过度表达睫状神经营养因子（CNTF）的转基因小鼠、将CNTF直接注射到脑实质以及通过腺病毒载体异位表达CNTF的研究表明，CNTF可激活星形胶质细胞。矛盾的是，迄今为止的研究未能显示CNTF对培养的星形胶质细胞中胶质纤维酸性蛋白（GFAP）表达的影响。因此，本研究的目的是利用核肥大和GFAP表达作为胶质细胞激活的指标，比较前脑1型和2型星形胶质细胞对CNTF的反应性。正如其他人所报道的，CNTF不会增加1型星形胶质细胞中的GFAP；然而，它会使其核大小迅速增加20%。在接触CNTF后4小时内核肥大就很明显，并持续至少48小时。相比之下，在CNTF处理48小时的过程中，2型星形胶质细胞的GFAP增加了2倍。在同一处理期间，2型星形胶质细胞核增大了25%。我们得出结论，CNTF直接刺激1型和2型星形胶质细胞。连同我们的体内研究（Levison等人，1996年：《实验神经病学》141:256），这些数据支持了CNTF导致中枢神经系统损伤和疾病后出现的许多渐进性星形胶质细胞变化这一概念。
