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Volume 17, Number 19, Issue of October 1, 1997 pp. 7228-7236
Copyright ©1997 Society for Neuroscience

Phenotypic Alteration of Astrocytes Induced by Ciliary Neurotrophic Factor in the Intact Adult Brain, As Revealed by Adenovirus-Mediated Gene Transfer

Received March 26, 1997; revised June 12, 1997; accepted July 10, 1997.

Fabrice Lisovoski¹, Said Akli², Elise Peltekian¹, Emmanuelle Vigne³, Georg Haase², Michel Perricaudet³, Patrick A. Dreyfus¹, Axel Kahn², and Marc Peschanski¹

¹ Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale Unité 421, Institut Mondor de Médecine Moléculaire, Institut Gustave Roussy, 94010 Créteil Cedex, France, ² Institut National de la Santé et de la Recherche Médicale Unité 129, Institut Cochin de Genetique Moleculaire, 75014 Paris, France, and ³ Centre National de la Recherche Scientifique, Unité de Recherche Associée 1301/Rhône-Poulenc Rorer, Institut Mondor de Médecine Moléculaire, Institut Gustave Roussy, 94805 Villejuif Cedex, France

Synthesis of the ciliary neurotrophic factor (CNTF) and its specific receptor (CNTFR) is widespread in the intact CNS, but potential biological roles for this system remain elusive. Contradictory results have been obtained concerning a possible effect on the morphological and biochemical phenotype of astrocytes. To reassess this question, we have taken advantage of adenovirus-mediated gene transfer into the rat brain to obtain the local release of CNTF. Stereotaxic administration of CNTF recombinant adenovirus vectors into the striatum led to phenotypic changes in astrocytes located in regions that were related axonally to striatal neurons at the injection site. Astrocytes appeared hypertrophied and displayed an increase in both GFAP and CNTF immunoreactivity. This response was observed up to 5 weeks after injection, the longest time studied. It was not observed after the administration of a control vector. The methodology used in the present study, allowing us to analyze the effect of the factor in areas remote from the injection site, has provided conclusive evidence that CNTF affects the astroglial phenotype in the intact CNS. The characteristics of these effects may explain why contradictory results have been obtained previously, because this signaling system seems to have a low efficiency and therefore requires a high local concentration of the factor close to the target cells. One might speculate as to the involvement of a CNTF astroglio-astroglial signaling system in the organized response of a population of astrocytes to changes in CNS homeostasis detected locally, even by a single cell.

Key words: CNTF; adenovirus vector; astroglial differentiation; in vivo gene transfer; astrogliosis

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