Estradiol protects against oxygen and glucose deprivation in rat hippocampal organotypic cultures and activates Akt and inactivates GSK-3beta.
Here we investigated the neuroprotective effect of 17beta-estradiol in an in vitro model of ischemia. We used organotypic hippocampal slice cultures, acute or chronically treated with 17beta-estradiol (10 nM), and exposed to oxygen and glucose deprivation (OGD). Cellular death was quantified by measuring uptake of propidium iodide (PI), a marker of dead cells. In OGD exposed cultures, treated only with vehicle, about 70% of the CA1 area of hippocampus was labeled with PI, indicating a great percentage of cellular death. When cultures were treated with 17beta-estradiol (acute or chronically), this cellular death was reduced to 15%. This effect was prevented by LY294002 but was not by PD98059. Immunoblotting revealed that both, chronic and acute, treatments with 17beta-estradiol induced the phosphorylation/activation of Akt and the phosphorylation/inactivation of GSK-3beta. Our results show a clear neuroprotective effect of 17beta-estradiol and suggest that this effect could involve PI3-K pathway.
Cimarosti
Helena
H
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, 90035-003 Porto Alegre, RS, Brazil.
Zamin
Lauren L
LL
Frozza
Rudimar
R
Nassif
Melissa
M
Horn
Ana Paula
AP
Tavares
Alexandre
A
Netto
Carlos Alexandre
CA
Salbego
Christianne
C
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000502:physiology*; D000860:Hypoxia / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011419:Propidium; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
D004958:Estradiol; D005947:Glucose; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D011419:Propidium; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494920:Akt1 protein, rat; C000605508:Gsk3b protein, rat