Androgen Receptor Overexpression Is Neuroprotective in Experimental Stroke

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

Research output: Contribution to journalReview article

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)346-357
Number of pages12
JournalTranslational Stroke Research
Volume2
Issue number3
DOIs
StatePublished - Sep 1 2011

Keywords

  • Androgen receptor
  • Cerebral ischemia
  • DHT
  • PC12
  • Stroke
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Ayala, P., Uchida, M., Akiyoshi, K., Cheng, J., Hashimoto, J., Jia, T., Ronnekleiv, O. K., Murphy, S. J., Wiren, K. M., & Hurn, P. D. (2011). Androgen Receptor Overexpression Is Neuroprotective in Experimental Stroke. Translational Stroke Research, 2(3), 346-357. https://doi.org/10.1007/s12975-011-0079-z