While current dopamine-based drugs seem to be effective for most Parkinson's disease (PD) motor dysfunctions, they produce variable responsiveness for resting tremor. This lack of consistency could be explained by considering recent evidence suggesting that PD resting tremor can be divided into different partially overlapping phenotypes based on the dopamine response. These phenotypes may be associated with different pathophysiological mechanisms produced by a cortical-subcortical network involving even non-dopaminergic areas traditionally not directly related to PD. In this paper, we propose a bio-constrained computational model to study the neural mechanisms underlying a possible type of PD tremor: the one mainly involving the serotoninergic system. The simulations run with the model demonstrate that a physiological serotonin increase can partially recover dopamine levels at the early stages of the disease before the manifestation of overt tremor. This result suggests that monitoring serotonin concentration changes could be critical for early diagnosis. The simulations also show the effectiveness of a new pharmacological treatment for tremor that acts on serotonin to recover dopamine levels. This latter result has been validated by reproducing existing data collected with human patients.

中文翻译：

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增加血清素以减少帕金森震颤

虽然目前基于多巴胺的药物似乎对大多数帕金森病 (PD) 运动功能障碍有效，但它们对静息性震颤产生不同的反应。这种缺乏一致性可以通过考虑最近的证据来解释，这些证据表明 PD 静息性震颤可以根据多巴胺反应分为不同的部分重叠表型。这些表型可能与皮层-皮层下网络产生的不同病理生理机制有关，甚至涉及传统上与 PD 没有直接关系的非多巴胺能区域。在本文中，我们提出了一种生物约束计算模型来研究一种可能类型的 PD 震颤的神经机制：主要涉及 5-羟色胺能系统。使用该模型运行的模拟表明，生理血清素的增加可以在疾病的早期阶段在明显震颤表现之前部分恢复多巴胺水平。这一结果表明，监测血清素浓度变化可能对早期诊断至关重要。模拟还显示了一种新的震颤药物治疗的有效性，该药物作用于血清素以恢复多巴胺水平。后一个结果已通过复制人类患者收集的现有数据得到验证。模拟还显示了一种新的震颤药物治疗的有效性，该药物作用于血清素以恢复多巴胺水平。后一个结果已通过复制人类患者收集的现有数据得到验证。模拟还显示了一种新的震颤药物治疗的有效性，该药物作用于血清素以恢复多巴胺水平。后一个结果已通过复制人类患者收集的现有数据得到验证。