Nonsteroidal Selective Androgen Receptor Modulators and Selective Estrogen Receptor β Agonists Moderate Cognitive Deficits and Amyloid-β Levels in a Mouse Model of Alzheimer's Disease.
George, Sonia LU ; Petit, Géraldine LU ; Gouras, Gunnar LU
; Brundin, Patrik
LU
and Olsson, Roger
LU
(2013)
In ACS Chemical Neuroscience
4(12).
p.1537-1548
- Abstract
- Decreases of the sex steroids, testosterone and estrogen, are associated with increased risk of Alzheimer's disease. Testosterone and estrogen supplementation improves cognitive deficits in animal models of Alzheimer's disease. Sex hormones play a role in the regulation of amyloid-β via induction of the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of dihydrotestosterone (DHT), we administered a selective androgen receptor agonist, ACP-105, alone and in combination with the selective estrogen receptor β (ERβ) agonist AC-186 to male gonadectomized triple transgenic mice. We assessed long-term spatial memory in the Morris water maze, spontaneous locomotion, and anxiety-like behavior in the open... (More)
- Decreases of the sex steroids, testosterone and estrogen, are associated with increased risk of Alzheimer's disease. Testosterone and estrogen supplementation improves cognitive deficits in animal models of Alzheimer's disease. Sex hormones play a role in the regulation of amyloid-β via induction of the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of dihydrotestosterone (DHT), we administered a selective androgen receptor agonist, ACP-105, alone and in combination with the selective estrogen receptor β (ERβ) agonist AC-186 to male gonadectomized triple transgenic mice. We assessed long-term spatial memory in the Morris water maze, spontaneous locomotion, and anxiety-like behavior in the open field and in the elevated plus maze. We found that ACP-105 given alone decreases anxiety-like behavior. Furthermore, when ACP-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloid-β levels in the brain as well as improve cognition. Interestingly, the androgen receptor level in the brain was increased by chronic treatment with the same combination treatment, ACP-105 and AC-186, not seen with DHT or ACP-105 alone. Based on these results, the beneficial effect of the selective ERβ agonist as a potential therapeutic for Alzheimer's disease warrants further investigation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4066133
- author
- George, Sonia
LU
; Petit, Géraldine
LU
; Gouras, Gunnar
LU
; Brundin, Patrik
LU
and Olsson, Roger
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- ACS Chemical Neuroscience
- volume
- 4
- issue
- 12
- pages
- 1537 - 1548
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000328864900005
- pmid:24020966
- scopus:84890649872
- ISSN
- 1948-7193
- DOI
- 10.1021/cn400133s
- language
- English
- LU publication?
- yes
- id
- 7fe785d3-2ab5-44d0-a967-994836d2b9c2 (old id 4066133)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24020966?dopt=Abstract
- date added to LUP
- 2016-04-01 13:57:48
- date last changed
- 2022-04-22 00:38:36
@article{7fe785d3-2ab5-44d0-a967-994836d2b9c2,
abstract = {{Decreases of the sex steroids, testosterone and estrogen, are associated with increased risk of Alzheimer's disease. Testosterone and estrogen supplementation improves cognitive deficits in animal models of Alzheimer's disease. Sex hormones play a role in the regulation of amyloid-β via induction of the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of dihydrotestosterone (DHT), we administered a selective androgen receptor agonist, ACP-105, alone and in combination with the selective estrogen receptor β (ERβ) agonist AC-186 to male gonadectomized triple transgenic mice. We assessed long-term spatial memory in the Morris water maze, spontaneous locomotion, and anxiety-like behavior in the open field and in the elevated plus maze. We found that ACP-105 given alone decreases anxiety-like behavior. Furthermore, when ACP-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloid-β levels in the brain as well as improve cognition. Interestingly, the androgen receptor level in the brain was increased by chronic treatment with the same combination treatment, ACP-105 and AC-186, not seen with DHT or ACP-105 alone. Based on these results, the beneficial effect of the selective ERβ agonist as a potential therapeutic for Alzheimer's disease warrants further investigation.}},
author = {{George, Sonia and Petit, Géraldine and Gouras, Gunnar and Brundin, Patrik and Olsson, Roger}},
issn = {{1948-7193}},
language = {{eng}},
number = {{12}},
pages = {{1537--1548}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Chemical Neuroscience}},
title = {{Nonsteroidal Selective Androgen Receptor Modulators and Selective Estrogen Receptor β Agonists Moderate Cognitive Deficits and Amyloid-β Levels in a Mouse Model of Alzheimer's Disease.}},
url = {{http://dx.doi.org/10.1021/cn400133s}},
doi = {{10.1021/cn400133s}},
volume = {{4}},
year = {{2013}},
}