Effects of high-intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis

Effects of high-intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis
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DOI:
10.1002/mus.20004
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发表时间:
2004-05-01
期刊:
影响因子:
3.4
通讯作者:
Tarnopolsky, MA
Tarnopolsky, MA
中科院分区:
医学3区
文献类型:
--
作者:
Mahoney, DJ;Rodriguez, C;Tarnopolsky, MA

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G93A 转基因小鼠的铜/锌超氧化物歧化酶 (CuZnSOD) 发生突变,导致氧化应激和运动神经元损失。众所周知,耐力运动训练可以提高骨骼肌的抗氧化能力。因此,我们假设耐力训练可能会延长 G93A 小鼠的疾病发作或生存期。我们研究了高强度耐力运动训练(45 分钟/天,5 次/周,从 9 m/min 逐渐增加到 22 m/min)对 G93A 小鼠疾病发作和存活的影响。耐力训练不影响临床发病,尽管它加速了雄性小鼠的死亡(P < 0.05)。接受耐力训练的男性在第 112 天时转棒表现出现统计学显着下降(P < 0.05),而久坐的男性在第 119 天时下降(P < 0.05)。接受耐力训练和久坐的女性分别在第 126 天和第 129 天下降(P < 0.05)。雌性小鼠的寿命比雄性小鼠长(P < 0.05),并且雄性小鼠有临床发病加速的趋势(P = 0.062)。我们得出的结论是,高强度耐力运动训练不会影响 G93A 小鼠临床症状的出现,但仅会加速雄性小鼠运动表现的下降和临床症状出现后的死亡。根据最近的一份报告,描述低强度耐力训练后存活率增加,看来训练强度是 G93A 小鼠存活率的重要决定因素。
The G93A transgenic mouse has a mutation in copper/zinc superoxide dismutase (CuZnSOD) that results in oxidative stress and motor neuron loss. Endurance exercise training is known to increase antioxidant capacity in skeletal muscle. Therefore, we hypothesized that endurance training may extend onset of disease or survival in the G93A mouse. We examined the effects of high-intensity endurance exercise training (45 min/ day, 5 times/week, progressive increase from 9 to 22 m/min) on disease onset and survival in G93A mice. Endurance training did not affect clinical onset, although it hastened death in male mice (P < 0.05). Endurance-trained males had a statistically significant decrease in rotarod performance at 112 days (P < 0.05), whereas sedentary males decreased at 119 days (P < 0.05). Endurance-trained and sedentary females decreased at 126 days and 129 days, respectively (P < 0.05). Female mice lived longer than males (P < 0.05), and there was a trend for hastened clinical onset in males (P = 0.062). We conclude that high-intensity endurance exercise training does not affect onset of clinical symptoms in G93A mice but hastens a decrease in motor performance and death following onset of clinical symptoms in male mice only. In light of a recent report describing increased survival following low-intensity endurance training, it appears that training intensity is an important determinant of survival in the G93A mouse.