突触可塑性可能是 l-DOPA 诱导运动障碍的基础。
Synaptic plasticity may underlie l-DOPA induced dyskinesia.
机构信息
Departments of Neurology, Columbia University Medical Center and Division of Molecular Therapeutics, New York State Psychiatric Institute, United States.
Departments of Psychiatry, Pharmacology, Columbia University Medical Center and Division of Molecular Therapeutics, New York State Psychiatric Institute, United States.
出版信息
Curr Opin Neurobiol. 2018 Feb;48:71-78. doi: 10.1016/j.conb.2017.10.021. Epub 2017 Nov 7.
Abstract
l-DOPA provides highly effective treatment for Parkinson's disease, but l-DOPA induced dyskinesia (LID) is a very debilitating response that eventually is presented by a majority of patients. A central issue in understanding the basis of LID is whether it is due to a response to chronic l-DOPA over years of therapy, and/or due to synaptic changes that follow the loss of dopaminergic neurotransmission and then triggered by acute l-DOPA administration. We review recent work that suggests that specific synaptic changes in the D1 dopamine receptor-expressing direct pathway striatal projection neurons due to loss of dopamine in Parkinson's disease are responsible for LID. Chronic l-DOPA may nevertheless modulate LID through priming mechanisms.
摘要
左旋多巴为帕金森病提供了非常有效的治疗方法，但左旋多巴诱导的运动障碍（LID）是一种非常虚弱的反应，最终大多数患者都会出现。理解 LID 基础的一个核心问题是，它是由于多年治疗中对慢性左旋多巴的反应，还是由于多巴胺能神经传递丧失后引起的突触变化，然后由急性左旋多巴给药触发。我们回顾了最近的工作，这些工作表明，帕金森病中由于多巴胺丧失导致 D1 多巴胺受体表达的直接通路纹状体投射神经元中的特定突触变化是导致 LID 的原因。然而，慢性左旋多巴可能通过启动机制来调节 LID。
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