Effects of global ischemia and estradiol pretreatment on phosphorylation of Akt, CREB and STAT3 in hippocampal CA1 of young and middle-aged female rats

M. De Butte-Smith, R. Suzanne Zukin, A. M. Etgen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Whereas long term treatment of middle-aged female rats with estradiol at physiological doses ameliorates neuronal death, the signaling pathways that mediate the neuroprotection are, as yet, unknown. Protein kinase B (Akt) and downstream transcription factors, the cAMP response element binding protein (CREB) and signal transducer and activator of transcription (STAT3) are critical players in cellular survival following injury. The present study was undertaken to determine whether long term estradiol alters the phosphorylation status and activity of Akt, STAT3 and CREB in ovariohysterectomized, middle-aged and young female rats subjected to global ischemia. Irrespective of either hormone or ischemic condition, middle-aged females exhibited lower levels of p-CREB and higher levels of Akt and STAT3 in CA1 than young females, as assessed by Western blot. In middle-aged animals, ischemia increased the phosphorylation status/activity of Akt and STAT3, and decreased the phosphorylation status/activity of CREB in the hippocampal CA1. Whereas estradiol did not detectably alter the phosphorylation status/activity of Akt or STAT3, it prevented the ischemia-induced decrease in nuclear p-CREB. Similar results were observed for the young females. Collectively, these data demonstrate that CREB, STAT3, and Akt are involved in the molecular response to global ischemia and that age influences the status of CREB, STAT3 and Akt activity in CA1 under physiological as well as pathological conditions, further emphasizing the importance of including older rodents in neuroprotection studies.

Original languageEnglish (US)
Pages (from-to)118-128
Number of pages11
JournalBrain Research
Volume1471
DOIs
StatePublished - Aug 30 2012

Fingerprint

Cyclic AMP Response Element-Binding Protein
Estradiol
Ischemia
Phosphorylation
Proto-Oncogene Proteins c-akt
Pyramidal Cells
Transducers
Rodentia
Transcription Factors
Western Blotting
Hormones
Wounds and Injuries

Keywords

  • Akt
  • cAMP response element binding protein
  • Estradiol
  • Global ischemia
  • Hippocampus
  • Neuroprotection
  • Ovariectomy
  • Signal transducer and activator of transcription-3

ASJC Scopus subject areas

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

Cite this

Effects of global ischemia and estradiol pretreatment on phosphorylation of Akt, CREB and STAT3 in hippocampal CA1 of young and middle-aged female rats. / De Butte-Smith, M.; Zukin, R. Suzanne; Etgen, A. M.

In: Brain Research, Vol. 1471, 30.08.2012, p. 118-128.

Research output: Contribution to journalArticle

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