Estrogen Pretreatment of Organotypic Hippocampal Slices Protects Neurons against Oxygen-Glucose Deprivation with Akt Activation

  • Park, Eun-Mi (Department of Pharmacology, College of Medicine, Ewha Womans University) ;
  • Park, Sung-Hui (Department of Pharmacology, College of Medicine, Ewha Womans University) ;
  • Lee, Kyung-Eun (Department of Pharmacology, College of Medicine, Ewha Womans University) ;
  • Published : 2006.06.21

Abstract

In several experimental models, estrogens protect neurons against ischemic insults. However, the recent clinical studies of hormone replacement showed negative results to prevent stroke. Therefore, optimal models to study estrogen replacement for neuroprotection are needed before its clinical ap-plication. Organotypic hippocampal slice under oxygen-glucose deprivation (OGD) has been established as a model of cerebral ischemia and has advantages to study drug effects. We investigated whether estrogen protected CAI neurons and affected activation of Akt (pAkt) in CAI region under OGD. Thus, rat hippocampal slices on day 7 of culture were treated with $17-{\beta}$ estradiol (E, 1 nM) for 7 days before 30 min OGD, and cell death of CAI neurons was quantified by propidium iodide (PI) staining and expression of pAkt was studied by Western blot and immunofluorescence. PI intensity in slices treated with E was significantly reduced 72 hour after OGD compared to that of non-treated slices (p < 0.05). E pretreatment also increased the expression of pAkt 72 hour after OGD compared to that of no treatment (p<0.01). These data suggest that estrogen pretreatment may rescue neurons from ischemic insults through the activation of Akt and also indicate that our model would be a useful alternative method to study the mechanisms and effects of estrogen replacement treatment for neuroprotection.

Keywords

References

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