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Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen–glucose deprivation and reperfusion

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Abstract

As a response to central nervous system injury, astrocytes become reactive. Two cellular hallmarks of reactive gliosis are hypertrophy of astrocyte processes and upregulation of intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP), vimentin, nestin, and synemin. Astrocytes in mice devoid of GFAP and vimentin (GFAP −/− Vim −/−) do not form cytoplasmic intermediate filaments. GFAP −/− Vim −/− mice develop larger infarcts after ischemic stroke (Li et al. in J Cereb Blood Flow Metab 28(3):468–481, 2008). Here, we attempted to analyze the underlying mechanisms using oxygen–glucose deprivation (OGD), an in vitro ischemia model, examining a potential link between astrocyte intermediate filaments and reactive oxygen species (ROS). We observed a reorganization of the intermediate filament network in astrocytes exposed to OGD. ROS accumulation was higher in GFAP −/− Vim −/− than wild-type astrocytes when exposed to OGD followed by reperfusion or when exposed to hydrogen peroxide. These results indicate that the elimination of ROS is impaired in the absence of the intermediate filament system. Compared to wild-type astrocytes, GFAP −/− Vim −/− astrocytes exposed to OGD and reperfusion exhibited increased cell death and conferred lower degree of protection to cocultured neurons. We conclude that the astrocyte intermediate filament system is important for the cell response to oxidative stress induced by OGD followed by reperfusion.

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Acknowledgments

We thank Dr. Ulrika Wilhelmsson and Dr. Noriko Shinjyo for their comments on the manuscript and Anna Stokowska for help with the statistical analysis. This work was supported by the Swedish Medical Research Council (project 11548), AFA Research Foundation, ALF Göteborg (project 11392), Sten A. Olsson Foundation for Research and Culture, Söderberg Foundations, Hjärnfonden, the Swedish Stroke Foundation, the Swedish Society for Medical Research, the Free Mason Foundation, Amlöv’s Foundation, E. Jacobson’s Donation Fund, NanoNet COST Action (BM1002), the EU FP 7 Program EduGlia (237956), and the EU FP 7 Program TargetBraIn (279017).

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  1. Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 9A, Gothenburg, 413 90, Sweden

    Yolanda de Pablo, Michael Nilsson, Marcela Pekna & Milos Pekny

  2. Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 440, Gothenburg, 405 30, Sweden

    Yolanda de Pablo & Milos Pekny

  3. Hunter Medical Research Institute, Newcastle, Australia

    Michael Nilsson

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  1. Yolanda de Pablo
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Correspondence to Yolanda de Pablo or Milos Pekny.

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de Pablo, Y., Nilsson, M., Pekna, M. et al. Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen–glucose deprivation and reperfusion. Histochem Cell Biol 140, 81–91 (2013). https://doi.org/10.1007/s00418-013-1110-0

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