Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, Paraná, Brasil.
J Neurosci Res. 2013 Nov;91(11):1508-16. doi: 10.1002/jnr.23258. Epub 2013 Aug 1.
The recently described intranigral rotenone model of Parkinson's disease (PD) in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. The relevance of this model remains unexplored with regard to sleep disorders that occur in PD. On this basis, the construction of a PD model depicting several behavioral and neurochemical alterations related to sleep would be helpful in understanding the association between PD and sleep regulation. We performed bilateral intranigral injections of rotenone (12 μg) on day 0 and the open-field test initially on day 20 after rotenone. Acquisition phase of the object-recognition test, executed also during day 20, was followed by an exact period of 24 hr of rapid eye movement (REM) sleep deprivation (REMSD; day 21). In the subsequent day (22), the rats were re-exposed to the open-field test and to the object-recognition test (choice phase). After the last session of behavioral tests, the rat brains were immediately dissected, and their striata were collected for neurochemical purposes. We observed that a brief exposure to REMSD was able to impair drastically the object-recognition test, similarly to a nigrostriatal lesion promoted by intranigral rotenone. However, the combination of REMSD and rotenone surprisingly did not inflict memory impairment, concomitant with a moderate compensatory mechanism mediated by striatal dopamine release. In addition, we demonstrated the existence of changes in serotonin and noradrenaline neurotransmissions within the striatum mostly as a function of REMSD and REMSD plus rotenone, respectively.
最近在啮齿动物中描述的黑质内 rotenone 帕金森病 (PD) 模型为研究毒素诱导的多巴胺能神经元损伤的机制提供了一个有趣的模型。关于 PD 中发生的睡眠障碍，该模型的相关性仍未得到探索。在此基础上，构建一个描绘与睡眠相关的几种行为和神经化学改变的 PD 模型，将有助于理解 PD 和睡眠调节之间的关联。我们在 rotenone （12μg）注射的第 0 天和 rotenone 注射后的第 20 天进行双侧黑质内注射，并在第 20 天进行旷场测试。物体识别测试的获得阶段也在第 20 天进行，随后进行 24 小时快速眼动 (REM) 睡眠剥夺 (REMSD; 第 21 天)。在随后的第 22 天，大鼠再次进行旷场测试和物体识别测试（选择阶段）。在最后一次行为测试后，立即解剖大鼠大脑，并收集其纹状体进行神经化学研究。我们观察到，短暂的 REMSD 暴露能够严重损害物体识别测试，类似于黑质内 rotenone 引起的黑质纹状体损伤。然而，令人惊讶的是，REMSD 和 rotenone 的组合并没有造成记忆损伤，同时伴随着纹状体多巴胺释放介导的适度补偿机制。此外，我们证明了纹状体中 5-羟色胺和去甲肾上腺素神经传递的变化，主要是作为 REMSD 和 REMSD 加 rotenone 的函数。
