Iwamoto Konosuke, Yoshii Yasuhiro, Ikeda Ken
Department of Neurology, Toho University Omori Medical Center, 6-11-1 Omorinishi, Otaku, Tokyo, Japan.
Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):405-9. doi: 10.3109/17482960902870993.
We aimed to study whether atorvastatin treatment can retard motor neuron degeneration in wobbler mice. Wobbler mice and their normal littermates were fed 0.01% atorvastatin-mixed food (10 mg/kg/day) or regular food from age 3-4 weeks of disease onset for four weeks (n=10/group) or more than eight weeks (n=10/group). Motor function was evaluated by pull-strength and deformity scale of the forelimbs. For those symptomatic assessment and body weight were measured weekly. Neuropathological and biochemical changes of the biceps muscle and the cervical cord were analyzed at four weeks after treatment. Compared to vehicle, atorvastatin-treated wobbler mice delayed progression of forelimb motor deficits by more than four weeks. Wobbler mice significantly increased body weight from three weeks post-treatment of atorvastatin, compared with vehicle (p<0.05). Atorvastatin administration suppressed denervation atrophy at 30% (p<0.01), maintained choline acetyl transferase activities of the biceps muscle (p<0.05), and attenuated approximately 30% loss of motor neurons in wobbler mice (p<0.01). Atorvastatin fed to normal littermates did not influence body weight gain, neuropathological and biochemical findings. These data suggest that atorvastatin has neuroprotective effects on denervating muscles and degenerating motor neurons in wobbler mice.
我们旨在研究阿托伐他汀治疗是否能延缓震颤小鼠运动神经元的退化。从疾病发作3 - 4周龄开始,将震颤小鼠及其正常同窝小鼠喂食0.01%阿托伐他汀混合食物(10毫克/千克/天)或普通食物,持续四周(每组n = 10)或超过八周(每组n = 10)。通过前肢的拉力和畸形程度来评估运动功能。对于那些有症状的小鼠,每周测量其症状和体重。在治疗四周后分析二头肌和颈髓的神经病理学和生化变化。与对照组相比,阿托伐他汀治疗的震颤小鼠前肢运动功能障碍的进展延迟了超过四周。与对照组相比,阿托伐他汀治疗后三周,震颤小鼠体重显著增加(p<0.05)。给予阿托伐他汀可抑制30%的失神经萎缩(p<0.01),维持二头肌的胆碱乙酰转移酶活性(p<0.05),并使震颤小鼠运动神经元损失减少约30%(p<0.01)。喂食正常同窝小鼠阿托伐他汀对体重增加、神经病理学和生化结果没有影响。这些数据表明,阿托伐他汀对震颤小鼠失神经支配的肌肉和退化的运动神经元具有神经保护作用。