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

doi:10.1016/j.yhbeh.2017.11.015

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 journal › Article › Research › peer-review

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 language	English
Pages (from-to)	16-21
Number of pages	6
Journal	Hormones and Behavior
Volume	98
DOIs	https://doi.org/10.1016/j.yhbeh.2017.11.015
State	Published - 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

Tschiffely, A. E., Schuh, R. A., Prokai-Tatrai, K., Ottinger, M. A., & Prokai, L. (2018). An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease. Hormones and Behavior, 98, 16-21. https://doi.org/10.1016/j.yhbeh.2017.11.015

Tschiffely, Anna E. ; Schuh, Rosemary A. ; Prokai-Tatrai, Katalin ; Ottinger, Mary Ann ; Prokai, Laszlo. / An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease. In: Hormones and Behavior. 2018 ; Vol. 98. pp. 16-21.

@article{289552a6b1f64fc29336ca8be19076c6,

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.",

keywords = "Alzheimer's disease, Brain-selective prodrug, Estradiol, Learning, Male double-transgenic mice",

author = "Tschiffely, {Anna E.} and Schuh, {Rosemary A.} and Katalin Prokai-Tatrai and Ottinger, {Mary Ann} and Laszlo Prokai",

year = "2018",

month = "2",

day = "1",

doi = "10.1016/j.yhbeh.2017.11.015",

language = "English",

volume = "98",

pages = "16--21",

journal = "Hormones and Behavior",

issn = "0018-506X",

publisher = "Academic Press Inc.",

}

Tschiffely, AE, Schuh, RA, Prokai-Tatrai, K, Ottinger, MA & Prokai, L 2018, 'An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease', Hormones and Behavior, vol. 98, pp. 16-21. https://doi.org/10.1016/j.yhbeh.2017.11.015

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 journal › Article › Research › peer-review

TY - JOUR

T1 - An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease

AU - Tschiffely, Anna E.

AU - Schuh, Rosemary A.

AU - Prokai-Tatrai, Katalin

AU - Ottinger, Mary Ann

AU - Prokai, Laszlo

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Brain-selective prodrug

KW - Estradiol

KW - Learning

KW - Male double-transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=85036671004&partnerID=8YFLogxK

U2 - 10.1016/j.yhbeh.2017.11.015

DO - 10.1016/j.yhbeh.2017.11.015

M3 - Article

VL - 98

SP - 16

EP - 21