title: Altered astrocytic swelling in the cortex of α-syntrophin-negative GFAP/EGFP mice.
abstract: Brain edema accompanying ischemic or traumatic brain injuries, originates from a disruption of ionic/neurotransmitter homeostasis that leads to accumulation of K(+) and glutamate in the extracellular space. Their increased uptake, predominantly provided by astrocytes, is associated with water influx via aquaporin-4 (AQP4). As the removal of perivascular AQP4 via the deletion of α-syntrophin was shown to delay edema formation and K(+) clearance, we aimed to elucidate the impact of α-syntrophin knockout on volume changes in individual astrocytes in situ evoked by pathological stimuli using three dimensional confocal morphometry and changes in the extracellular space volume fraction (α) in situ and in vivo in the mouse cortex employing the real-time iontophoretic method. RT-qPCR profiling was used to reveal possible differences in the expression of ion channels/transporters that participate in maintaining ionic/neurotransmitter homeostasis. To visualize individual astrocytes in mice lacking α-syntrophin we crossbred GFAP/EGFP mice, in which the astrocytes are labeled by the enhanced green fluorescent protein under the human glial fibrillary acidic protein promoter, with α-syntrophin knockout mice. Three-dimensional confocal morphometry revealed that α-syntrophin deletion results in significantly smaller astrocyte swelling when induced by severe hypoosmotic stress, oxygen glucose deprivation (OGD) or 50 mM K(+). As for the mild stimuli, such as mild hypoosmotic or hyperosmotic stress or 10 mM K(+), α-syntrophin deletion had no effect on astrocyte swelling. Similarly, evaluation of relative α changes showed a significantly smaller decrease in α-syntrophin knockout mice only during severe pathological conditions, but not during mild stimuli. In summary, the deletion of α-syntrophin markedly alters astrocyte swelling during severe hypoosmotic stress, OGD or high K(+).
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Department of Neuroscience, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Anderova
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Benesova
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Mikesova
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Dzamba
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Honsa
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kriska
authors.affiliation: Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Olena
authors.initials: O
authors.lastname: Butenko
authors.affiliation: Laboratory of Gene Expression, Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Novosadova
authors.affiliation: Laboratory of Gene Expression, Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Valihrach
authors.affiliation: Laboratory of Gene Expression, Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Mikael
authors.initials: M
authors.lastname: Kubista
authors.affiliation: Department of Neuroscience, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
authors.forename: Lesia
authors.initials: L
authors.lastname: Dmytrenko
authors.affiliation: Department of Neuroscience, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Cicanic
authors.affiliation: Department of Neuroscience, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
authors.forename: Lydia
authors.initials: L
authors.lastname: Vargova
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D001929:Brain Edema / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein; D005947:Glucose / Q000172:deficiency; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008867:Microtomy; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013238:Stereotaxic Techniques; D046509:Tissue Culture Techniques
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; C485184:enhanced green fluorescent protein; C528900:glial fibrillary astrocytic protein, mouse; C091825:syntrophin alpha1; D049452:Green Fluorescent Proteins; D005947:Glucose; D011188:Potassium