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

• When adult GFAP+ astrocytes are depleted in vivo, motor skills are severely impaired
• Neuronal loss occurs, whereas astroglial structural support still persists
• Astroglial dysfunction disrupts CNS redox homeostasis, independent of microgliosis
• Neutralization of ROS/RNS protects from neuronal injury

SummaryAlthough 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.

Graphical AbstractFigure optionsDownload as PowerPoint slide