Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson's disease.
Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson's disease.
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DOI：
10.1038/npjparkd.2016.1
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Barrantes FJ
中科院分区：
文献类型：
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作者：
Perez-Lloret S;Barrantes FJ
鉴于其能够解释帕金森病（PD）最常见的运动症状，多巴胺能神经元的变性被认为是该疾病的主要病理生理学特征之一。多项研究表明，神经变性还会影响去甲肾上腺素能、血清素能、胆碱能和其他单胺能神经元群。在这项工作中，回顾了帕金森病胆碱能缺陷的特征及其临床相关性。多种运动和认知功能的重要神经生理过程在突触、通路和回路水平上转移到胆碱能神经传递。大量证据强调胆碱能改变与帕金森病运动症状、步态功能障碍、左旋多巴引起的运动障碍、认知恶化、精神病、睡眠异常、自主神经功能障碍和嗅觉功能改变之间的联系。这些症状的病理生理学与纹状体胆碱能张力的改变和/或胆碱能核的变性有关，最重要的是大细胞基底核和桥脚核。一些结果表明，抗毒蕈碱药物可用于治疗帕金森病运动症状，乙酰胆碱酯酶抑制剂可用于治疗痴呆。数据还表明，这些抑制剂和桥脚核深部脑刺激也可能有效预防跌倒。最后，几种作用于烟碱受体的药物已被证明可有效治疗左旋多巴引起的运动障碍和认知障碍，并可作为帕金森病动物模型中的神经保护剂。人类患者的结果仍然缺乏。
In view of its ability to explain the most frequent motor symptoms of Parkinson’s Disease (PD), degeneration of dopaminergic neurons has been considered one of the disease’s main pathophysiological features. Several studies have shown that neurodegeneration also affects noradrenergic, serotoninergic, cholinergic and other monoaminergic neuronal populations. In this work, the characteristics of cholinergic deficits in PD and their clinical correlates are reviewed. Important neurophysiological processes at the root of several motor and cognitive functions remit to cholinergic neurotransmission at the synaptic, pathway, and circuital levels. The bulk of evidence highlights the link between cholinergic alterations and PD motor symptoms, gait dysfunction, levodopa-induced dyskinesias, cognitive deterioration, psychosis, sleep abnormalities, autonomic dysfunction, and altered olfactory function. The pathophysiology of these symptoms is related to alteration of the cholinergic tone in the striatum and/or to degeneration of cholinergic nuclei, most importantly the nucleus basalis magnocellularis and the pedunculopontine nucleus. Several results suggest the clinical usefulness of antimuscarinic drugs for treating PD motor symptoms and of inhibitors of the enzyme acetylcholinesterase for the treatment of dementia. Data also suggest that these inhibitors and pedunculopontine nucleus deep-brain stimulation might also be effective in preventing falls. Finally, several drugs acting on nicotinic receptors have proved efficacious for treating levodopa-induced dyskinesias and cognitive impairment and as neuroprotective agents in PD animal models. Results in human patients are still lacking.