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
N1 - Funding Information:
This research was supported by the National Institutes of Health grants AG031387 (MAO), AG031535 and CA215550 (LP), and EY027005 (KPT), as well as by the Robert A. Welch Foundation (endowment BK-0031 , LP), the VA Research Service Rehabilitation R&D REAP (RAS), the Biomedical R&D CDA02 (RAS), and was conducted in partial fulfillment of the Ph.D. requirements for the University of Maryland (AET). L.P. and K.P.-T. have equity interests in AgyPharma LLC and are co-inventors of US Patents 7,026,306 and 7,300,926 on the use of DHED. All other authors disclose no financial interest or potential conflicts of interest.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/2
Y1 - 2018/2
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
C2 - 29183688
AN - SCOPUS:85036671004
SN - 0018-506X
VL - 98
SP - 16
EP - 21
JO - Hormones and Behavior
JF - Hormones and Behavior
ER -