Acute estradiol protects CA1 neurons from ischemia-induced apoptotic cell death via the PI3K/Akt pathway

Teresa Jover-Mengual, Takahiro Miyawaki, Adrianna Latuszek, Enrique Alborch, R. Suzanne Zukin, Anne M. Etgen

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Exogenous estradiol ameliorates global ischemia-induced neuronal death and cognitive impairment in male and female rodents. However, the molecular mechanisms by which a single acute injection of estradiol administered after the ischemic event intervenes in global ischemia-induced apoptotic cell death are unclear. Here we show that acute estradiol acts via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling cascade to protect CA1 neurons in ovariectomized female rats. We demonstrate that global ischemia promotes early activation of glycogen synthase kinase-3β (GSK3β) and forkhead transcription factor of the O class (FOXO)3A, known Akt targets that are related to cell survival, and activation of caspase-3. Estradiol prevents ischemia-induced dephosphorylation and activation of GSK3β and FOXO3A, and the caspase death cascade. These findings support a model whereby estradiol acts by activation of PI3K/Akt signaling to promote neuronal survival in the face of global ischemia.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalBrain Research
Volume1321
DOIs
StatePublished - Mar 19 2010

Fingerprint

1-Phosphatidylinositol 4-Kinase
Estradiol
Cell Death
Ischemia
Neurons
Glycogen Synthase Kinase 3
Forkhead Transcription Factors
Proto-Oncogene Proteins c-akt
Caspases
Heart Arrest
Caspase 3
Thoracic Surgery
Rodentia
Cell Survival
Injections

Keywords

  • Apoptosis
  • Estradiol
  • Global ischemia
  • Neuronal death
  • PI3K/Akt/signaling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Acute estradiol protects CA1 neurons from ischemia-induced apoptotic cell death via the PI3K/Akt pathway. / Jover-Mengual, Teresa; Miyawaki, Takahiro; Latuszek, Adrianna; Alborch, Enrique; Zukin, R. Suzanne; Etgen, Anne M.

In: Brain Research, Vol. 1321, 19.03.2010, p. 1-12.

Research output: Contribution to journalArticle

Jover-Mengual, Teresa ; Miyawaki, Takahiro ; Latuszek, Adrianna ; Alborch, Enrique ; Zukin, R. Suzanne ; Etgen, Anne M. / Acute estradiol protects CA1 neurons from ischemia-induced apoptotic cell death via the PI3K/Akt pathway. In: Brain Research. 2010 ; Vol. 1321. pp. 1-12.
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