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Horm Behav. 2018 Feb;98:16-21. doi: 10.1016/j.yhbeh.2017.11.015. Epub 2017 Dec 22.

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

Author information

1
Neuroscience and Cognitive Science Graduate Program, University of Maryland College Park, MD 20742, USA; Department of Animal and Avian Sciences, University of Maryland College Park, MD 20742, USA.
2
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Research Service, VAMHCS, Baltimore, MD 21201, USA.
3
Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
4
Department of Animal and Avian Sciences, University of Maryland College Park, MD 20742, USA. Electronic address: maotting@central.uh.edu.
5
Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. Electronic address: Laszlo.Prokai@unthsc.edu.

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.

KEYWORDS:

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

PMID:
29183688
PMCID:
PMC5999339
DOI:
10.1016/j.yhbeh.2017.11.015
[Indexed for MEDLINE]
Free PMC Article

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