The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective

Roberta Diaz Brinton, Shuhua Chen, Marissa Montoya, Debra Hsieh, Jasmin Minaya, Jeffrey Kim, Hsiao Pai Chu

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens (CEEs), the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women's Health Initiative. Morphologic analyses demonstrated that CEEs significantly increased neuronal outgrowth in hippocampal, basal forebrain, occipital, parietal and frontal cortex neurons. Dose-response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect with greatest potency occurring in hippocampal and occipital cortex neurons. CEES induced highly significant neuroprotection against beta amyloid25-35, hydrogen peroxide and glutamate-induced toxicity. Rank order of potency and magnitude of CEE-induced neuroprotection in the brain regions investigated was hippocampal neurons > basal forebrain neurons > cortical neurons. In hippocampal neurons pre-exposed to beta amyloid25-35, CEEs halted Aβ25-35-induced cell death and protected surviving neurons from further cell death induced by Aβ25-35. Because CEEs are the estrogen replacement therapy of the Women's Health Initiative, results of the current study could provide cellular mechanisms for understanding effects of CEEs on cognitive function and risk of Alzheimer's disease derived from this prospective clinical trial. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)475-496
Number of pages22
JournalNeurobiology of Aging
Volume21
Issue number3
DOIs
StatePublished - May 2000
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Basal forebrain
  • Cerebral cortex
  • Conjugated equine estrogens
  • Estrogen
  • Estrogen replacement therapy
  • Hippocampus
  • Neuroprotection
  • Neurotrophism
  • Premarin

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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