Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease
Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease
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DOI：
10.1172/jci42642
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发表时间：
2010-08-01
影响因子：
15.9
通讯作者：
Francois, Chantal
中科院分区：
文献类型：
--
作者：
Karachi, Carine;Grabli, David;Francois, Chantal
步态障碍和姿势不稳是帕金森病(PD)老年患者常见的症状，对用于治疗其他帕金森症状的多巴胺能药物反应较差。帕金森病和衰老中步态障碍和跌倒的大脑结构仍有待研究。在健康受试者的功能磁共振成像中，我们发现由桥脚核(PPN)和相邻的楔状核组成的中脑运动区(MLR)的活动受到想象步态速度的调节，而更快的想象步态激活了MLR内的一个离散的簇。此外，帕金森病患者和因MPTP中毒而出现帕金森病的老年猴子的步态障碍与PPN胆碱能神经元的丢失有关。损毁双侧PPN的胆碱能部分可导致非多巴胺能损毁猴子的步态和姿势缺陷。因此，我们的数据显示，PPN的胆碱能神经元在控制步态和姿势方面起着中心作用，可能是帕金森病患者步态障碍的药物治疗的靶点。
Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.