CILIARY NEUROTROPHIC FACTOR STIMULATES NUCLEAR HYPERTROPHY AND INCREASES THE GFAP CONTENT OF CULTURED ASTROCYTES

Studies using transgenic mice that overexpress ciliary neurotrophic fa ctor (CNTF), direct injection of CNTF into brain parenchyma, and ectop ic expression of CNTF by an adenoviral vector have demonstrated that C NTF activates astrocytes. Paradoxically, studies to date have failed t o show an effect of CNTF on the expression of GFAP by cultured astrocy tes. Therefore, the goal of this study was to use nuclear hypertrophy and GFAP expression as indices of glial activation to compare the resp onsiveness of forebrain type 1 and type 2 astrocytes to CNTF. As repor ted by others, CNTF did not increase GFAP in type 1 astrocytes; howeve r, it rapidly increased their nuclear size by 20%. Nuclear hypertrophy was apparent within 4 h after CNTF exposure and persisted for at leas t 48 h. In contrast, type 2 astrocyte GFAP increased 2-fold over the c ourse of 48 h of CNTF treatment. During this same treatment period typ e 2 astroglial nuclei enlarged by 25%. We conclude that CNTF stimulate s both type 1 and type 2 astrocytes directly. Together with our in viv o studies (Levison et al., 1996: Exp. Neurol. 141: 256), these data su pport the concept that CNTF is responsible for many of the progressive astroglial changes that appear after CNS injury and disease. (C) 1998 Elsevier Science B.V. All rights reserved.