PHENOTYPIC ALTERATION OF ASTROCYTES INDUCED BY CILIARY NEUROTROPHIC FACTOR IN THE INTACT ADULT BRAIN, AS REVEALED BY ADENOVIRUS-MEDIATED GENE-TRANSFER

Synthesis of the ciliary neurotrophic factor (CNTF) and its specific r eceptor (CNTFR alpha) is widespread in the intact CNS, but potential b iological roles for this system remain elusive. Contradictory results have been obtained concerning a possible effect on the morphological a nd 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 pheno typic changes in astrocytes located in regions that were related axona lly to striatal neurons at the injection site. Astrocytes appeared hyp ertrophied and displayed an increase in both GFAP and CNTF immunoreact ivity. This response was observed up to 5 weeks after injection, the l ongest time studied. It was not observed after the administration of a control vector. The methodology used in the present study, allowing u s to analyze the effect of the factor in areas remote from the injecti on site, has provided conclusive evidence that CNTF affects the astrog lial 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 there fore requires a high local concentration of the factor close to the ta rget cells. One might speculate as to the involvement of a CNTF astrog lio-astroglial signaling system in the organized response of a populat ion of astrocytes to changes in CNS homeostasis detected locally, even by a single cell.