Gonadectomy and dehydroepiandrosterone (DHEA) do not modulate disease progression in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis
Gonadectomy and dehydroepiandrosterone (DHEA) do not modulate disease progression in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis
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DOI：
10.3109/17482968.2012.654393
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发表时间：
2012-05-01
影响因子：
--
通讯作者：
Suzuki, Masatoshi
中科院分区：
文献类型：
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作者：
Hayes-Punzo, Antonio;Mulcrone, Patrick;Suzuki, Masatoshi
流行病学研究表明，男性肌萎缩侧索硬化症（ALS）的发病率高于女性。有趣的是，在过表达突变的人类超氧化物歧化酶-1 （SOD1-G93A）的家族性ALS啮齿动物模型中，疾病的发病和进展存在明显的性别差异。在本研究中，我们试图确定通过性腺切除术或慢性神经保护神经类固醇治疗血清类固醇水平的改变是否可以调节ALS大鼠模型（SOD1-G93A转基因大鼠）的疾病发生和进展。对症状前的SOD1-G93A大鼠进行性腺切除术或使用硅胶管植入神经类固醇脱氢表雄酮（DHEA）治疗。采用BBB （Basso-Beattie-Bresnahan）评分对运动测试进行常规分析，确定动物的发病和进展情况。虽然在完整的和去性腺的SOD1-G93A大鼠中观察到两性异形，但性腺切除术对疾病的发生和进展没有显著影响。脱氢表雄酮治疗没有改变SOD1-G93A大鼠的疾病进展或生存。我们的研究结果表明，性腺类固醇或神经类固醇不是ALS大鼠模型中发生或疾病进展的可能调节剂之一。进一步的分析将是必要的，以了解性别二态性是如何参与ALS疾病进展的。
Epidemiological studies have shown a higher incidence of amyotrophic lateral sclerosis (ALS) in men than women. Interestingly, there are clear gender differences in disease onset and progression in rodent models of familial ALS overexpressing mutated human superoxide dismutase-1 (SOD1-G93A). In the present study we sought to determine whether the alterations of serum steroid levels by gonadectomy or chronic treatment of neuroprotective neurosteroids can modulate disease onset and progression in a rat model of ALS (SOD1-G93A transgenic rats). Presymptomatic SOD1-G93A rats were gonadectomized or treated with a neurosteroid dehydroepiandrosterone (DHEA) using silastic tubing implants. Disease onset and progression of the animals were determined by the routine analyses of locomotor testing using the Basso-Beattie-Bresnahan (BBB) score. Although sexual dimorphism was observed in intact and gonadectomized SOD1-G93A rats, there was no significant effect of gonadectomy on disease onset and progression. DHEA treatment did not alter disease progression or survival in SOD1-G93A rats. Our results indicate that gonadal steroids or neurosteroids are not one of the possible modulators for the occurrence or disease progression in a rat model of ALS. Further analysis will be necessary to understand how sexual dimorphism is involved in ALS disease progression.