An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease

Anna E. Tschiffely, Rosemary A. Schuh, Katalin Prokai-Tatrai, Mary Ann Ottinger, Laszlo Prokai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Estrogens are neuroprotective, and studies suggest that they may mitigate the pathology and symptoms of Alzheimer's disease (AD) in female models. However, central estrogen effects have not been examined in males in the context of AD. The purpose of this follow-up study was to assess the benefits of a brain-selective 17β-estradiol estrogen prodrug, 10β,17β-hydroxyestra-1,4-dien-3-one (DHED), also in the male APPswe/PS1dE9 double-transgenic mouse model of the disease. After continuously exposing 6-month old animals to DHED for two months, their brains showed decreased amyloid precursor and amyloid-β protein levels. The DHED-treated APPswe/PS1dE9 double transgenic subjects also exhibited enhanced performance in a cognitive task, while 17β-estradiol treatment did not reach statistical significance. Taken together, data presented here suggest that DHED may also have therapeutic benefit in males and warrant further investigations to fully elucidate the potential of targeted estrogen therapy for a gender-independent treatment of early-stage AD.

Original languageEnglish
Pages (from-to)16-21
Number of pages6
JournalHormones and Behavior
Volume98
DOIs
StatePublished - 1 Feb 2018

Fingerprint

Alzheimer Disease
Estrogens
Brain
Estradiol
Amyloid beta-Protein Precursor
Prodrugs
Amyloid
Transgenic Mice
Pathology
3,16-dihydroxyandrost-5-ene-17,19-dione
Therapeutics

Keywords

  • Alzheimer's disease
  • Brain-selective prodrug
  • Estradiol
  • Learning
  • Male double-transgenic mice

Cite this

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title = "An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease",
abstract = "Estrogens are neuroprotective, and studies suggest that they may mitigate the pathology and symptoms of Alzheimer's disease (AD) in female models. However, central estrogen effects have not been examined in males in the context of AD. The purpose of this follow-up study was to assess the benefits of a brain-selective 17β-estradiol estrogen prodrug, 10β,17β-hydroxyestra-1,4-dien-3-one (DHED), also in the male APPswe/PS1dE9 double-transgenic mouse model of the disease. After continuously exposing 6-month old animals to DHED for two months, their brains showed decreased amyloid precursor and amyloid-β protein levels. The DHED-treated APPswe/PS1dE9 double transgenic subjects also exhibited enhanced performance in a cognitive task, while 17β-estradiol treatment did not reach statistical significance. Taken together, data presented here suggest that DHED may also have therapeutic benefit in males and warrant further investigations to fully elucidate the potential of targeted estrogen therapy for a gender-independent treatment of early-stage AD.",
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An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease. / Tschiffely, Anna E.; Schuh, Rosemary A.; Prokai-Tatrai, Katalin; Ottinger, Mary Ann; Prokai, Laszlo.

In: Hormones and Behavior, Vol. 98, 01.02.2018, p. 16-21.

Research output: Contribution to journalArticle

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