Pagano Gennaro, Yousaf Tayyabah, Politis Marios
Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 125 Coldharbour Lane, London, Camberwell, SE5 9NU, UK.
Curr Neurol Neurosci Rep. 2017 Oct 3;17(11):90. doi: 10.1007/s11910-017-0794-2.
To review the current status of positron emission tomography (PET) molecular imaging research of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD).
Recent PET studies have provided robust evidence that LIDs in PD are associated with elevated and fluctuating striatal dopamine synaptic levels, which is a consequence of the imbalance between dopaminergic and serotonergic terminals, with the latter playing a key role in mishandling presynaptic dopamine release. Long-term exposure to levodopa is no longer believed to solely induce LIDs, as studies have highlighted that PD patients who go on to develop LIDs exhibit elevated putaminal dopamine release before the initiation of levodopa treatment, suggesting the involvement of other mechanisms, including altered neuronal firing and abnormal levels of phosphodiesterase 10A. Dopaminergic, serotonergic, glutamatergic, adenosinergic and opioid systems and phosphodiesterase 10A levels have been shown to be implicated in the development of LIDs in PD. However, no system may be considered sufficient on its own for the development of LIDs, and the mechanisms underlying LIDs in PD may have a multisystem origin. In line with this notion, future studies should use multimodal PET molecular imaging in the same individuals to shed further light on the different mechanisms underlying the development of LIDs in PD.
回顾帕金森病（PD）中左旋多巴诱导的异动症（LIDs）的正电子发射断层扫描（PET）分子成像研究现状。
近期的PET研究提供了有力证据，表明PD中的LIDs与纹状体多巴胺突触水平升高和波动有关，这是多巴胺能和5-羟色胺能终末之间失衡的结果，后者在处理突触前多巴胺释放不当方面起关键作用。长期接触左旋多巴不再被认为是单独诱发LIDs的原因，因为研究强调，继续发展为LIDs的PD患者在开始左旋多巴治疗前壳核多巴胺释放就已升高，这表明其他机制也参与其中，包括神经元放电改变和磷酸二酯酶10A水平异常。多巴胺能、5-羟色胺能、谷氨酸能、腺苷能和阿片样物质系统以及磷酸二酯酶10A水平已被证明与PD中LIDs的发生有关。然而，没有一个系统单独就足以导致LIDs的发生，PD中LIDs的潜在机制可能有多个系统起源。与此观点一致，未来的研究应在同一患者中使用多模态PET分子成像，以进一步阐明PD中LIDs发生的不同机制。
