The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias.
The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias.
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DOI：
10.1016/j.nbd.2021.105491
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发表时间：
2021-11
影响因子：
6.1
通讯作者：
Subramanian T
中科院分区：
文献类型：
--
作者：
Iyer V;Venkiteswaran K;Savaliya S;Lieu CA;Handly E;Gilmour TP;Kunselman AR;Subramanian T
帕金森病 (PD) 是一种神经退行性运动障碍，常规使用左旋多巴治疗。不幸的是，使用左旋多巴的长期多巴胺替代疗法会导致左旋多巴诱发的运动障碍（LID），这是一种显着且致残的副作用。临床结果表明，LID 通常仅在 PD 运动症状从单侧（Hoehn 和 Yahr (HY) I 期）进展到双侧期（HY II 期）后发生。这表明存在一些延迟 LID 发生的补偿性半球间机制。因此，我们研究了黑质纹状体通路的半球间连接对 PD 大鼠模型中 LID 表达的作用。首先向大鼠一个半球的纹状体注射逆行示踪剂，以标记同侧和跨半球的黑质纹状体通路。然后将大鼠分成几组，并在注射示踪剂的半球的纹状体或内侧前脑束中进行单侧损伤，以诱导不同程度的偏侧帕金森症。最后，用左旋多巴治疗大鼠并测试LID的表达。经历了基于 LID 的相同损伤模式的大鼠中出现了不同的子集。引人注目的是，非运动障碍大鼠从未病变半球突出的跨半球黑质纹状体通路显着保留。相比之下，运动障碍大鼠只有一小部分该通路在损伤后幸存下来。至关重要的是，非运动障碍和运动障碍大鼠的同侧半球黑质纹状体通路存活率和帕金森运动缺陷的水平几乎相同。我们的数据表明，跨半球黑质纹状体通路的存活在阻止 LID 表达方面发挥着至关重要的作用，并且是阻止常见抗 PD 治疗的这种破坏性副作用进展的潜在新靶点。
Parkinson’s disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. Clinical findings indicate that LID typically only occurs following the progression of PD motor symptoms from the unilateral (Hoehn and Yahr (HY) Stage I) to the bilateral stage (HY Stage II). This suggests the presence of some compensatory interhemispheric mechanisms that delay the occurrence of LID. We therefore investigated the role of interhemispheric connections of the nigrostriatal pathway on LID expression in a rat model of PD. The striatum of one hemisphere of rats was first injected with a retrograde tracer to label the ipsi- and cross-hemispheric nigrostriatal pathways. Rats were then split into groups and unilaterally lesioned in the striatum or medial forebrain bundle of the tracer-injected hemisphere to induce varying levels of hemiparkinsonism. Finally, rats were treated with levodopa and tested for the expression of LID. Distinct subsets emerged from rats that underwent the same lesioning paradigm based on LID. Strikingly, non-dyskinetic rats had significant sparing of their cross-hemispheric nigrostriatal pathway projecting from the unlesioned hemisphere. In contrast, dyskinetic rats only had a small proportion of this pathway survive lesioning. Crucially, both non-dyskinetic and dyskinetic rats had nearly identical levels of ipsi-hemispheric nigrostriatal pathway survival and parkinsonian motor deficits. Our data suggest that the survival of the cross-hemispheric nigrostriatal pathway plays a crucial role in preventing the expression of LID and represents a potentially novel target to halt the progression of this devastating side-effect of a common anti-PD therapeutic.
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DOI：
10.1038/s41531-018-0069-x
发表时间：
2018
期刊：
NPJ Parkinson's disease
影响因子：
--
作者：
Eusebi P;Romoli M;Paoletti FP;Tambasco N;Calabresi P;Parnetti L
通讯作者：
Parnetti L
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
影响因子：
3
作者：
Blesa, Javier;Juri, Carlos;Obeso, Jose A.
通讯作者：
Obeso, Jose A.
DOI：
10.1007/bf01972287
发表时间：
1982-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
COLLINGRIDGE, GL
通讯作者：
COLLINGRIDGE, GL
影响因子：
4.1
作者：
Djamshidian, Atbin;Poewe, Werner
通讯作者：
Poewe, Werner