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 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.
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Division of Gene Expression and Development, Roslin Institute, Roslin, Midlothian, UK.
Allen
N D
ND
Skynner
M
M
Gusterson
B
B
Clark
A J
AJ
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001388:Aziridines / Q000494:pharmacology; D001921:Brain / Q000166:cytology*; D002470:Cell Survival / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D004926:Escherichia coli / Q000201:enzymology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009043:Motor Activity / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009601:Nitroreductases / Q000235:genetics / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology; D012016:Reference Values
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D001388:Aziridines; D005904:Glial Fibrillary Acidic Protein; D011355:Prodrugs; C100099:tretazicar; D009601:Nitroreductases