title: Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS.
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.
authors: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland; Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Bettina
authors: B
authors: Schreiner
authors: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, 81377 Munich, Germany.
authors: Elisa
authors: E
authors: Romanelli
authors: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, 92-101 Lodz, Poland.
authors: Pawel
authors: P
authors: Liberski
authors: Department of Pathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors: Barbara
authors: B
authors: Ingold-Heppner
authors: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland; Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Bettina
authors: B
authors: Sobottka-Brillout
authors: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors: Tom
authors: T
authors: Hartwig
authors: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Vijay
authors: V
authors: Chandrasekar
authors: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
authors: Helge
authors: H
authors: Johannssen
authors: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland.
authors: Hanns Ulrich
authors: HU
authors: Zeilhofer
authors: Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Adriano
authors: A
authors: Aguzzi
authors: Department of Neuropathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors: Frank
authors: F
authors: Heppner
authors: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
authors: Martin
authors: M
authors: Kerschensteiner
authors: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland. Electronic address: becher@immunology.uzh.ch.
authors: Burkhard
authors: B
authors: Becher
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D016923:Cell Death; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C528900:glial fibrillary astrocytic protein, mouse