Département de Neurochirurgie, Hôpital Pitie Salpêtrière, AP-HP, 75013, Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, APHP GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle épinière (ICM), 47, boulevard de l'Hôpital, 75013, Paris, France.
J Neural Transm (Vienna). 2018 Mar;125(3):471-483. doi: 10.1007/s00702-017-1678-y. Epub 2017 Jan 13.
Patients with Parkinson's disease (PD) develop cardinal motor symptoms, including akinesia, rigidity, and tremor, that are alleviated by dopaminergic medication and/or subthalamic deep brain stimulation. Over the time course of the disease, gait and balance disorders worsen and become resistant to pharmacological and surgical treatments. These disorders generate debilitating motor symptoms leading to increased dependency, morbidity, and mortality. PD patients also experience sleep disturbance that raise the question of a common physiological basis. An extensive experimental and clinical body of work has highlighted the crucial role of the pedunculopontine nucleus (PPN) in the control of gait and sleep, and its potential major role in PD. Here, we summarise our investigations in the monkey PPN in the normal and parkinsonian states. We first examined the anatomy and connectivity of the PPN and the cuneiform nucleus which both belong to the mesencephalic locomotor region. Second, we conducted experiments to demonstrate the specific effects of PPN cholinergic lesions on locomotion in the normal and parkinsonian monkey. Third, we aimed to understand how PPN cholinergic lesions impair sleep in parkinsonian monkeys. Our final goal was to develop a novel model of advanced PD with gait and sleep disorders. We believe that this monkey model, even if it does not attempt to reproduce the exact human disease with all its complexities, represents a good biomedical model to characterise locomotion and sleep in the context of PD.
帕金森病（PD）患者会出现运动障碍的主要症状，包括运动迟缓、僵硬和震颤，这些症状可以通过多巴胺能药物和/或丘脑底核深部脑刺激来缓解。随着疾病的发展，步态和平衡障碍会恶化，并对药物和手术治疗产生抗药性。这些障碍会导致致残的运动症状，增加依赖性、发病率和死亡率。PD 患者还会经历睡眠障碍，这引发了一个共同的生理基础的问题。大量的实验和临床工作强调了脑桥被盖核（PPN）在控制步态和睡眠方面的关键作用，以及它在 PD 中的潜在重要作用。在这里，我们总结了我们在正常和帕金森猴 PPN 中的研究。我们首先检查了 PPN 和楔形核的解剖和连接，它们都属于中脑运动区。其次，我们进行了实验，以证明 PPN 胆碱能损伤对正常和帕金森猴运动的特定影响。第三，我们旨在了解 PPN 胆碱能损伤如何损害帕金森猴的睡眠。我们的最终目标是开发一种具有步态和睡眠障碍的新型晚期 PD 模型。我们相信，即使这种猴子模型不能复制所有复杂性的精确人类疾病，它也代表了一个很好的生物医学模型，可以在 PD 背景下研究运动和睡眠。
