Investigation of the role of androgen receptor in functional recovery of mice with spinal cord injury

• Main Authors: Pei-Shan Lee, 李佩珊
• Other Authors: Liang-Yo Yang
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/17757675654025973708

碩士 === 臺北醫學大學 === 醫學科學研究所 === 96 === Severe spinal cord injuries (SCI) often cause loss of motor and sensory functions below the lesion site. Up to now, methylprednisolone (MP) is the only FDA-approved therapeutic agent for treating acute SCI, however, MP has only limited therapeutic effect accompanied by adverse side effects. Thus, it is imperative to develop or invent a better therapeutic agent or strategy to treat SCI. Some studies have reported that male SCI patients show a better recovery outcome than female SCI patients. Evidence also shows that androgen has a neuroprotective effect on injured neurons. It is widely accepted that androgen exerts its effects on cells via binding to androgen receptor. Based on the above findings, we propose the hypothesis that androgen receptor plays an important role in spinal cord injury. In this study, we employed transgenic mice with androgen receptor knockout (ARKO) in all cells ad their male littermates (4 months old) to test the effect of on the functional recovery of SCI. Spinal cord injury was induced by a force of 60 K dynes delivered by IH Impactor. The locomotor activity of mice was evaluated before and 1, 4, 7, 10, 14, 21, 28, and 35days after SCI. Moreover, the spinal lesion and the amount of remaining axons at the lesion site were assessed after sacrifice of SCI mice. Our results showed that male ARKO mice exhibited a worse functional recovery than the male wild-type littermates after SCI. In addition, SCI mice with ARKO showed a lager spinal lesion and had fewer preserved axons at the lesion site. These findings strongly suggest that androgen receptor exerts a beneficial effect on SCI.