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01-09-2011 | Review

Androgen Receptor Overexpression Is Neuroprotective in Experimental Stroke

Authors: Patricia Ayala, Masayoshi Uchida, Kozaburo Akiyoshi, Jian Cheng, Joel Hashimoto, Taiping Jia, Oline K. Ronnekleiv, Stephanie J. Murphy, Kristine M. Wiren, Patricia D. Hurn

Published in: Translational Stroke Research | Issue 3/2011

Abstract

Male sex is a known risk factor in human stroke. However, the role of the cognate receptor for androgens—the androgen receptor (AR)—in stroke outcome remains unclear. Here, we found that AR mRNA is downregulated in the peri-infarct tissue of gonadally intact male mice subjected to middle cerebral artery occlusion (MCAO) and 6 h reperfusion. We then used genetically engineered mice overexpressing AR in brain (AR-Tg) to compare outcomes from MCAO in intact or castrated males and to evaluate the neuroprotective role of dihydrotestosterone (DHT) replacement in AR-Tg castrates. A further evaluation of AR overexpression in ischemic paradigms was performed using rat PC12 cells transfected with human AR and treated with oxidative and apoptotic stressors. We then studied the role of DHT in cultures overexpressing AR. Our results show (1) ischemia alters the expression of AR by decreasing AR mRNA levels, (2) AR overexpression is protective in vivo against MCAO in intact and castrated AR-Tg mice and in vitro against oxidative and apoptotic stressors in AR-PC12 cells, and (3) DHT does not enhance the protection triggered by AR overexpression in AR-Tg castrated mice nor in AR-PC12 cells.

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Title: Androgen Receptor Overexpression Is Neuroprotective in Experimental Stroke
Authors: Patricia Ayala
Masayoshi Uchida
Kozaburo Akiyoshi
Jian Cheng
Joel Hashimoto
Taiping Jia
Oline K. Ronnekleiv
Stephanie J. Murphy
Kristine M. Wiren
Patricia D. Hurn
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: Translational Stroke Research / Issue 3/2011
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-011-0079-z

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Androgen Receptor Overexpression Is Neuroprotective in Experimental Stroke

Abstract

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Springer Medicine

Abstract

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