Androgen receptor overexpression is neuroprotective in experimental stroke
Patricia Ayala1, Masayoshi Uchida, Kozaburo Akiyoshi
1Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239-3098, USA, ayalap@ohsu.edu.
Translational Stroke Research
|December 11, 2013
Summary
Androgen receptor (AR) levels decrease after stroke. Overexpressing the androgen receptor (AR) in mice and cells protected against stroke and stress, but dihydrotestosterone (DHT) did not enhance this effect.
Area of Science:
- Neuroscience
- Endocrinology
- Stroke Research
Background:
- Male sex is a recognized risk factor for stroke.
- The specific role of the androgen receptor (AR) in stroke outcomes is not well understood.
- Androgen receptor (AR) mRNA levels are reduced in brain tissue following ischemic stroke.
Purpose of the Study:
- To investigate the neuroprotective role of the androgen receptor (AR) in stroke.
- To determine if dihydrotestosterone (DHT) enhances AR-mediated neuroprotection.
- To examine AR expression changes and functional effects in ischemic conditions.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in mice to induce ischemic stroke.
- Genetically engineered mice overexpressing AR (AR-Tg) and wild-type littermates.
- In vitro studies using rat PC12 cells transfected with human AR under oxidative and apoptotic stress.
Main Results:
- Ischemia significantly downregulated AR mRNA levels in peri-infarct brain tissue.
- AR overexpression conferred significant protection against MCAO in both intact and castrated AR-Tg mice.
- AR overexpression protected PC12 cells against oxidative and apoptotic stressors; DHT did not augment this protection.
Conclusions:
- Androgen receptor (AR) expression is altered by ischemia, with decreased mRNA levels observed.
- Overexpression of the androgen receptor (AR) provides neuroprotection in both in vivo and in vitro models of brain injury.
- Dihydrotestosterone (DHT) does not appear to enhance AR-mediated neuroprotection in the studied models.
