Effects of riluzole on combined MPTP+3-nitropropionic acid-induced mild to moderate striatonigral degeneration in mice
Effects of riluzole on combined MPTP+3-nitropropionic acid-induced mild to moderate striatonigral degeneration in mice
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DOI：
10.1007/s00702-004-0206-z
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Tison, F
中科院分区：
文献类型：
--
作者：
Diguet, E;Fernagut, PO;Tison, F
我们研究了利鲁唑（一种抗多巴胺能药物）影响MPTP + 3-硝基丙酸（3-NP）联合中毒后小鼠纹状体和黑质联合变性（SND）的持续神经元死亡过程的效力。我们使用了一种“神经元拯救”的策略，即在中毒结束后给予利鲁唑。在生理盐水组和利鲁唑组（10 mg/kg和20 mg/kg）中比较运动障碍、其恢复、运动和感觉运动整合任务的行为表现以及组织病理学结果，并按运动严重程度三胞胎匹配。虽然利鲁唑对粗大运动障碍、旋转杆任务、旷场动力学变量或横梁任务均未产生任何影响，但对杆测试中的表现有微妙影响。在黑质和背外侧纹状体细胞丢失和星形胶质细胞活化方面，利鲁唑治疗小鼠的组织病理学结局显著更好，具有剂量效应关系。因此，从组织病理学的角度来看，利鲁唑具有有限的“神经元拯救”性质，在小鼠中MPTP + 3-NP诱导的SND中具有细微的运动行为改善。
We investigated the potency of riluzole, an anti-glutamatergic drug, to affect ongoing neuronal death process following combined MPTP + 3-nitropropionic acid (3-NP) intoxication producing combined striatal and nigral degeneration (SND) in mice. We used a "neuronal rescue" strategy by administering riluzole after the end of intoxication. The motor disorder, its recovery, behavioral performances at motor and sensorimotor integration tasks and histopathological outcome were compared in the saline and riluzole groups (10 mg/kg and 20 mg/kg), matched by triplets for motor severity. While riluzole did not produce any effect on the gross motor disorder nor on rotarod task, open-field kinetic variables or on the traversing beam task, it had a subtle effect on the performances at the pole test. The histopathological outcome was significantly better in the riluzole-treated mice regarding both nigral and dorsolateral striatal cell loss and astroglial activation, with a dose-effect relationship. Thus, riluzole has limited "neuronal rescue" properties from an histopathological point of view with a subtle motor behavior improvement in a MPTP + 3-NP-induced SND in mice.