title: Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion.
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.
authors.affiliation: 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.depablo@neuro.gu.se
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Pablo
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007382:Intermediate Filaments / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis*; D015424:Reperfusion
chemical_list: D017382:Reactive Oxygen Species; D005947:Glucose; D010100:Oxygen