Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Brain Res. 2013 Jun 4;1513:103-16. doi: 10.1016/j.brainres.2013.03.029. Epub 2013 Mar 30.
Affective disorders and memory impairments precede the classical motor symptoms seen in Parkinson's disease (PD) and the currently approved antiparkinsonian agents do not alleviate the non-motor symptoms as well as the underlying dopaminergic neuron degeneration. On the other hand, there is increasing evidence that inflammation plays a key role in the pathophysiology of PD and that the anti-inflammatory actions of statins are related to their neuroprotective properties against different insults in the CNS. The present data indicates that the oral treatment with atorvastatin (10mg/kg/day), once a day during 7 consecutive days, was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1mg/nostril). Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover, atorvastatin was found to protect against the long-lasting motor deficits evaluated in activity chambers and the loss of dopaminergic neurons in the substantia nigra pars compacta observed at 21 days after i.n. MPTP administration. At this time, despite the absence of spatial memory deficits in the water maze and in concentrations of the cytokines TNF-α, IL-1β and IL-10 in striatum and hippocampus following i.n. MPTP administration, atorvastatin treatment resulted in a significant increase in the striatal and hippocampal levels of nerve growth factor (NGF). These findings reinforce and extend the notion of the neuroprotective potential of atorvastatin and suggest that it may represent a new therapeutic tool for the management of motor and non-motor symptoms of PD.
情感障碍和记忆损伤先于帕金森病（PD）的经典运动症状出现，而目前批准的抗帕金森药物不仅不能缓解非运动症状，也不能缓解潜在的多巴胺能神经元退化。另一方面，越来越多的证据表明炎症在 PD 的病理生理学中起着关键作用，他汀类药物的抗炎作用与其在中枢神经系统中对抗不同损伤的神经保护特性有关。目前的数据表明，阿托伐他汀（10mg/kg/天）的口服治疗，每天一次，连续 7 天，可以预防短期记忆损伤和抑郁样行为的大鼠评估在社会识别和强迫游泳试验分别在 7 天和 14 天，在单次鼻内（i.n.）给予 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）（1mg/鼻孔）后。重要的是，此时在开放场试验中，动物的运动活动没有观察到明显的变化。此外，阿托伐他汀被发现可以防止在活动室中评估的长期运动缺陷，以及在 i.n. MPTP 给药后 21 天观察到的黑质致密部多巴胺能神经元的丢失。此时，尽管在水迷宫中没有空间记忆缺陷，以及在 i.n. MPTP 给药后纹状体和海马中的细胞因子 TNF-α、IL-1β 和 IL-10 的浓度没有空间记忆缺陷，但阿托伐他汀治疗导致纹状体和海马神经生长因子（NGF）水平显著增加。这些发现加强并扩展了阿托伐他汀具有神经保护潜力的观点，并表明它可能代表一种治疗 PD 的运动和非运动症状的新治疗工具。
