Ramírez-López F et al.xlsx

Prolonged dopamine replacement therapy commonly leads to incapacitating movements known as L-DOPA-induced dyskinesias in Parkinson’s disease. Recently, transcranial magnetic stimulation has been used as a non-invasive therapy for motor symptoms and dyskinesias in this disease. Several studies suggest that the motor effects of transcranial magnetic stimulation might be the result of dopamine system modulation. Nevertheless, the mechanisms underlying transcranial magnetic stimulation are not thoroughly understood. In the present study, we investigated whether transcranial magnetic stimulation regulates cellular activation as shown by c- Fos immunoreactivity, on dopamine D1 receptor positive cells of the striatum and motor cortex of dyskinetic and naïve rats. Furthermore, we evaluated transcranial magnetic stimulation effect on dyskinesias along with its molecular marker, FosB and motor execution of hemiparkinsonian rats. Our results show that transcranial magnetic stimulation reduces c-Fos expression in dopamine D1 receptor positive cells in the striatum and motor cortex. In addition, this treatment significantly attenuated dyskinesias, an effect accompanied by a low expression of FosB in the striatum and the improvement of motor execution. This study proposes that transcranial magnetic stimulation might modulate the activity of dopamine D1 receptors containing cells in the motor cortex and striatum and highlights the therapeutic potential of this technique in Parkinson’s disease. However, further investigation is needed to examine the role of dopamine D2 receptors and other regions in the effects of this treatment.

帕金森病患者长期接受多巴胺替代疗法后，常出现致残性运动障碍，即左旋多巴诱发异动症（L-DOPA-induced dyskinesias）。近年来，经颅磁刺激（transcranial magnetic stimulation）被用作该疾病运动症状与异动症的非侵入性治疗手段。多项研究表明，经颅磁刺激的运动效应可能源于多巴胺系统的调控作用。然而，经颅磁刺激的作用机制尚未被完全阐明。本研究中，我们探究了经颅磁刺激是否可调控异动症模型大鼠与正常未处理大鼠的纹状体（striatum）及运动皮层（motor cortex）内多巴胺D1受体（dopamine D1 receptor）阳性细胞的细胞活化情况，以c-Fos免疫反应性作为评估指标。此外，我们还评估了经颅磁刺激对偏帕金森病大鼠异动症及其分子标志物FosB的影响，以及其运动执行能力。本研究结果显示，经颅磁刺激可降低纹状体与运动皮层内多巴胺D1受体阳性细胞的c-Fos表达水平。此外，该治疗可显著减轻异动症，此效应伴随纹状体FosB表达降低以及运动执行能力的改善。本研究提示，经颅磁刺激可调控运动皮层与纹状体中表达多巴胺D1受体的细胞活性，并凸显了该技术在帕金森病中的治疗潜力。不过，仍需开展进一步研究以明确多巴胺D2受体及其他脑区在该治疗效应中的作用。