Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain

To study the function of astrocytes in the adult brain, we have targeted th e expression of E. coli nitroreductase (NTR) to the astrocytes of transgeni c mice under the control of the GFAP promoter. The astrocytes expressing NT R were selectively ablated after administration of the prodrug CB1954, resu lting in motor discoordination. Histological examination showed that the re gion most affected in the brain was the cerebellum, in which the Bergmann g lia were eliminated and the granular neurons had degenerated. Specific effe cts were also noted on the dendrites of the Purkinje cells, and the junctio n between these neurons and granular layer was disrupted. Astrocyte ablatio n was associated with a dramatic decrease in the expression of glutamate tr ansporters, which may account for the degeneration of granular neurons sinc e the excitotoxic effects of glutamate result in a similar phenotype. These results provide the first evidence that astrocytes are important for the s urvival of neurons in the adult brain in vivo. (C) 2001 Wiley-Liss, Inc.