Rylander Ottosson Daniella, Lane Emma
Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University Lund, Sweden.
School of Pharmacy and Pharmaceutical Sciences, Cardiff University Cardiff, UK.
Front Cell Neurosci. 2016 Feb 8;10:16. doi: 10.3389/fncel.2016.00016. eCollection 2016.
One of the major symptoms of the neurodegenerative condition Parkinson's disease (PD) is a slowness or loss of voluntary movement, yet frustratingly therapeutic strategies designed to restore movement can result in the development of excessive abnormal movements known as dyskinesia. These dyskinesias commonly develop as a result of pharmacotherapy in the form of L-DOPA administration, but have also been identified following deep brain stimulation (DBS) and intrastriatal cell transplantation. In the case of L-DOPA these movements can be treatment limiting, and whilst they are not long lasting or troubling following DBS, recognition of their development had a near devastating effect on the field of cell transplantation for PD.Understanding the relationship between these therapeutic approaches and the development of dyskinesia may improve our ability to restore function without disabling side effects. Interestingly, despite the fact that dopaminergic cell transplantation repairs many of the changes induced by the disease process and through L-DOPA treatment, there appears to be a relationship between the two. In rodent models of the disease, the severity of dyskinesia induced by L-DOPA prior to the transplantation procedure correlated with post-transplantation, graft-induced dyskinesia. A review of clinical data also suggested that the worse preoperational dyskinesia causes worsened graft-induced dyskinesia (GID). Understanding how these aberrant behaviors come about has been of keen interest to open up these therapeutic options more widely and one major underlying theory is the effects of these approaches on the plasticity of synapses within the basal ganglia. This review uniquely brings together developments in understanding the role of striatal synaptic plasticity in both L-DOPA and GID to guide and stimulate further investigations on the important striatal plasticity.
神经退行性疾病帕金森病（PD）的主要症状之一是自主运动迟缓或丧失，然而令人沮丧的是，旨在恢复运动的治疗策略可能会导致出现称为运动障碍的过度异常运动。这些运动障碍通常是左旋多巴给药形式的药物治疗的结果，但在深部脑刺激（DBS）和纹状体内细胞移植后也已被发现。就左旋多巴而言，这些运动可能会限制治疗，虽然它们在DBS后不会持续很长时间或造成困扰，但认识到它们的出现对PD细胞移植领域产生了近乎毁灭性的影响。了解这些治疗方法与运动障碍发展之间的关系可能会提高我们在不产生致残副作用的情况下恢复功能的能力。有趣的是，尽管多巴胺能细胞移植修复了许多由疾病过程和左旋多巴治疗引起的变化，但两者之间似乎存在关联。在该疾病的啮齿动物模型中，移植手术前左旋多巴诱导的运动障碍严重程度与移植后移植物诱导的运动障碍相关。对临床数据的回顾也表明，术前运动障碍越严重，移植物诱导的运动障碍（GID）就越严重。了解这些异常行为是如何产生的一直是人们非常感兴趣的，以便更广泛地开辟这些治疗选择，一个主要的潜在理论是这些方法对基底神经节内突触可塑性的影响。这篇综述独特地汇集了在理解纹状体突触可塑性在左旋多巴和GID中的作用方面的进展，以指导和刺激对重要的纹状体可塑性的进一步研究。
