Abstract Context L-DOPA is the first-line drug for Parkinson’s disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. Objectives This study determined changes in terms of neurodegeneration, locomotion and mechanosensation in Caenorhabditis elegans (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. Materials and methods Neurodegeneration was monitored via fluorescence microscopy of GFP-tagged dopaminergic neurons in the head and tail regions of C. elegans. Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60 mM), caffeine (10 mM) or 60 mM L-DOPA + 10 or 20 mM caffeine (60LC10 and 60LC20) treatments were scored for 3 days (n = 20). Results L-DOPA (60 mM) reduced CEP and ADE neurons by 4.3% on day 3, with a concomitant decrease in fluorescence by 44.6%. This correlated with reductions in gentle head (−35%) and nose touch (−40%) responses, but improved locomotion (20–75%) compared with vehicle alone. CEP and ADE neuron counts were preserved with caffeine (10 mM) or 60LC10 (98–100%), which correlated with improved mechanosensation (10–23%) and locomotion (18–76%). However, none of the treatments was able to preserve PDE neuron count, reducing the basal slowing response. Discussion and conclusions Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

中文翻译：

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咖啡因减少左旋多巴引起的机械感觉和运动缺陷，并保护帕金森病转基因秀丽隐杆线虫模型中的多巴胺能神经元


摘要背景左旋多巴是治疗帕金森病（PD）的一线药物。然而，长期使用会导致运动障碍。咖啡因是一种已知的神经保护剂，可以作为辅助剂来最大限度地减少左旋多巴的副作用。目的 本研究确定了过表达酪氨酸羟化酶 (CAT-2) 的秀丽隐杆线虫 (Rhabditidae) 菌株 UA57 在接受咖啡因、左旋多巴或其组合治疗时神经变性、运动和机械感觉方面的变化。材料和方法通过线虫头部和尾部区域的 GFP 标记的多巴胺能神经元的荧光显微镜监测神经变性。同时，对媒介物 (0.1% DMSO)、L-DOPA (60 mM)、咖啡因 (10 mM) 或 60 mM L-DOPA + 10 或 20 mM 咖啡因（60LC10 和 60LC20）治疗 3 天的机械感觉和运动进行评分（ n = 20）。结果 L-DOPA (60 mM) 在第 3 天使 CEP 和 ADE 神经元减少 4.3%，同时荧光减少 44.6%。与单独使用车辆相比，这与轻柔头部（−35%）和鼻子触摸（−40%）反应的减少相关，但运动能力改善（20-75%）。使用咖啡因 (10 mM) 或 60LC10 (98-100%) 保留 CEP 和 ADE 神经元计数，这与机械感觉 (10-23%) 和运动 (18-76%) 的改善相关。然而，没有一种治疗能够保留 PDE 神经元数量，从而减少基础减慢反应。讨论和结论 综上所述，我们表明咖啡因可以保护 DAergic 神经元，并在与 L-DOPA 共同给药时减少异常运动和感觉丧失，这可能会影响 PD 治疗并值得进一步研究。