1. Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS.
- Author
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Schreiner B, Romanelli E, Liberski P, Ingold-Heppner B, Sobottka-Brillout B, Hartwig T, Chandrasekar V, Johannssen H, Zeilhofer HU, Aguzzi A, Heppner F, Kerschensteiner M, and Becher B
- Subjects
- Animals, Antioxidants pharmacology, Brain cytology, Brain drug effects, Brain growth & development, Cell Death, Glial Fibrillary Acidic Protein genetics, Glial Fibrillary Acidic Protein metabolism, Mice, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism, Astrocytes metabolism, Brain metabolism, Motor Neurons metabolism, Oxidative Stress
- Abstract
Although the importance of reactive astrocytes during CNS pathology is well established, the function of astroglia in adult CNS homeostasis is less well understood. With the use of conditional, astrocyte-restricted protein synthesis termination, we found that selective paralysis of GFAP(+) astrocytes in vivo led to rapid neuronal cell loss and severe motor deficits. This occurred while structural astroglial support still persisted and in the absence of any major microvascular damage. Whereas loss of astrocyte function did lead to microglial activation, this had no impact on the neuronal loss and clinical decline. Neuronal injury was caused by oxidative stress resulting from the reduced redox scavenging capability of dysfunctional astrocytes and could be prevented by the in vivo treatment with scavengers of reactive oxygen and nitrogen species (ROS/RNS). Our results suggest that the subpopulation of GFAP(+) astrocytes maintain neuronal health by controlling redox homeostasis in the adult CNS., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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