Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS

Autor: 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
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Cell Reports, Vol 12, Iss 9, Pp 1377-1384 (2015)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2015.07.051
Popis: 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.
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