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Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain
Author(s) -
Cui Wei,
Allen Nicholas D.,
Skynner Michael,
Gusterson Barry,
Clark A. John
Publication year - 2001
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.1061
Subject(s) - astrocyte , biology , glutamate receptor , neuroscience , cerebellum , genetically modified mouse , neuroglia , transgene , central nervous system , microbiology and biotechnology , gene , receptor , biochemistry
To study the function of astrocytes in the adult brain, we have targeted the expression of E. coli nitroreductase (NTR) to the astrocytes of transgenic mice under the control of the GFAP promoter. The astrocytes expressing NTR were selectively ablated after administration of the prodrug CB1954, resulting in motor discoordination. Histological examination showed that the region most affected in the brain was the cerebellum, in which the Bergmann glia were eliminated and the granular neurons had degenerated. Specific effects were also noted on the dendrites of the Purkinje cells, and the junction between these neurons and granular layer was disrupted. Astrocyte ablation was associated with a dramatic decrease in the expression of glutamate transporters, which may account for the degeneration of granular neurons since the excitotoxic effects of glutamate result in a similar phenotype. These results provide the first evidence that astrocytes are important for the survival of neurons in the adult brain in vivo. GLIA 34:272–282, 2001. © 2001 Wiley‐Liss, Inc.