Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715008293 |
| _version_ | 1818984230852493312 |
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| author | Bettina Schreiner Elisa Romanelli Pawel Liberski Barbara Ingold-Heppner Bettina Sobottka-Brillout Tom Hartwig Vijay Chandrasekar Helge Johannssen Hanns Ulrich Zeilhofer Adriano Aguzzi Frank Heppner Martin Kerschensteiner Burkhard Becher |
| author_facet | Bettina Schreiner Elisa Romanelli Pawel Liberski Barbara Ingold-Heppner Bettina Sobottka-Brillout Tom Hartwig Vijay Chandrasekar Helge Johannssen Hanns Ulrich Zeilhofer Adriano Aguzzi Frank Heppner Martin Kerschensteiner Burkhard Becher |
| author_sort | Bettina Schreiner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T18:15:42Z |
| format | Article |
| id | doaj.art-7fd4a84eb2e94f8bbb87b77ec166f8a4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T18:15:42Z |
| publishDate | 2015-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7fd4a84eb2e94f8bbb87b77ec166f8a42022-12-21T19:30:23ZengElsevierCell Reports2211-12472015-09-011291377138410.1016/j.celrep.2015.07.051Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNSBettina Schreiner0Elisa Romanelli1Pawel Liberski2Barbara Ingold-Heppner3Bettina Sobottka-Brillout4Tom Hartwig5Vijay Chandrasekar6Helge Johannssen7Hanns Ulrich Zeilhofer8Adriano Aguzzi9Frank Heppner10Martin Kerschensteiner11Burkhard Becher12Institute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, 81377 Munich, GermanyDepartment of Molecular Pathology and Neuropathology, Medical University of Lodz, 92-101 Lodz, PolandDepartment of Pathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Neuropathology, University Hospital Zurich, 8091 Zurich, SwitzerlandInstitute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Neuropathology, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, 81377 Munich, GermanyInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandAlthough 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.http://www.sciencedirect.com/science/article/pii/S2211124715008293 |
| spellingShingle | Bettina Schreiner Elisa Romanelli Pawel Liberski Barbara Ingold-Heppner Bettina Sobottka-Brillout Tom Hartwig Vijay Chandrasekar Helge Johannssen Hanns Ulrich Zeilhofer Adriano Aguzzi Frank Heppner Martin Kerschensteiner Burkhard Becher Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS Cell Reports |
| title | Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS |
| title_full | Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS |
| title_fullStr | Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS |
| title_full_unstemmed | Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS |
| title_short | Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS |
| title_sort | astrocyte depletion impairs redox homeostasis and triggers neuronal loss in the adult cns |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715008293 |
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