Periodic 17β-Estradiol Pretreatment Protects Rat Brain from Cerebral Ischemic Damage via Estrogen Receptor-β

Ami Raval, Raquel Borges-Garcia, William Javier Moreno, Miguel Perez-Pinzon, Helen Bramlett

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Although chronic 17β-estradiol (E2) has been shown to be a cognition-preserving and neuroprotective agent in animal brain injury models, concern regarding its safety was raised by the failed translation of this phenomenon to the clinic. Previously, we demonstrated that a single bolus of E2 48 hr prior to ischemia protected the hippocampus from damage in ovariectomized rats via phosphorylation of cyclic-AMP response element binding protein, which requires activation of estrogen receptor subtype beta (ER-β). The current study tests the hypothesis that long-term periodic E2-treatment improves cognition and reduces post-ischemic hippocampal injury by means of ER-β activation. Ovariectomized rats were given ten injections of E2 at 48 hr intervals for 21 days. Hippocampal-dependent learning, memory and ischemic neuronal loss were monitored. Results demonstrated that periodic E2 treatments improved spatial learning, memory and ischemic neuronal survival in ovariectomized rats. Additionally, periodic ER-β agonist treatments every 48 hr improved post-ischemic cognition. Silencing of hippocampal ER-β attenuated E2-mediated ischemic protection suggesting that ER-β plays a key role in mediating the beneficial effects of periodic E2 treatments. This study emphasizes the need to investigate a periodic estrogen replacement regimen to reduce cognitive decline and cerebral ischemia incidents/impact in post-menopausal women.

Original languageEnglish
Article numbere60716
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 12 2013

Fingerprint

cognition
Estrogen Receptors
estradiol
Rats
Estradiol
Brain
pretreatment
Cognition
ischemia
brain
rats
learning
Brain models
Chemical activation
Data storage equipment
Cyclic AMP Response Element-Binding Protein
menopause
Phosphorylation
response elements
cyclic AMP

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Periodic 17β-Estradiol Pretreatment Protects Rat Brain from Cerebral Ischemic Damage via Estrogen Receptor-β. / Raval, Ami; Borges-Garcia, Raquel; Javier Moreno, William; Perez-Pinzon, Miguel; Bramlett, Helen.

In: PLoS One, Vol. 8, No. 4, e60716, 12.04.2013.

Research output: Contribution to journalArticle

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