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(+).
- MeSH
- akvaporin 4 genetika metabolismus MeSH
- astrocyty metabolismus patologie MeSH
- biologický transport MeSH
- draslík metabolismus MeSH
- draslíkové kanály genetika metabolismus MeSH
- edém mozku genetika metabolismus patologie MeSH
- glukosa nedostatek MeSH
- konfokální mikroskopie MeSH
- membránové proteiny nedostatek genetika MeSH
- mikrotomie MeSH
- mozková kůra metabolismus patologie MeSH
- myši transgenní MeSH
- myši MeSH
- osmolární koncentrace MeSH
- osmotický tlak MeSH
- promotorové oblasti (genetika) MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- proteiny vázající vápník nedostatek genetika MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- stereotaktické techniky MeSH
- svalové proteiny nedostatek genetika MeSH
- techniky tkáňových kultur MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH