Sci Transl Med：抑郁症等病是帕金森氏病治疗的一个路障

4月4日，国际著名杂志《科学转化医学》Science Translational Medicine在线刊登了国外研究人员的最新研究成果“Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson’s Patients Treated with Dopamine Grafts，”，文章中研究者表示抑郁症、疲劳等是帕金森氏病治疗的一个路障。

据一项新的研究报告，提高脑中的多巴胺水平可能不足以解决帕金森氏症患者中的非运动性症状，例如抑郁症和疲劳。除了严重的运动损害这一帕金森氏病的标志之外，该病还会引起显著影响生活品质的非运动性症状，诸如抑郁症、疲劳、视幻觉和睡眠问题。

Marios Politis及其同事们在此采集了在13-16年前移植了富含多巴胺的胚胎移植物的3名帕金森氏病患者的成像数据。这些人感受到了主要的运动技能的恢复并甚至停用左旋多巴达数年。不幸的是，即便他们的运动症状减少了，这些患者仍然得与抑郁症、疲劳和其它非运动性症状作斗争。研究人员对患者脑中的多巴胺神经元用放射性示踪剂进行了标记，并用一种叫做正电子发射断层扫描的成像技术显示，胚胎移植物恢复了多巴胺神经元的功能，从而带来患者运动技能的改善。然而，其它的用一种与产生5-羟色胺的神经元结合的显像剂所进行的脑扫描显示，在与调节睡眠、唤醒、食欲、情绪和情感有关的脑部区域中的5-羟色胺神经元数目低于正常。这些发现表明，多巴胺神经元替代疗法应该与其它的促进5-羟色胺的疗法相结合从而为患者提供针对帕金森氏病的更为完全的、长期的缓解。（生物谷Bioon.com）

doi:10.1126/scitranslmed.3003391
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Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson’s Patients Treated with Dopamine Grafts

Marios Politis1,*, Kit Wu1, Clare Loane1, Niall P. Quinn2, David J. Brooks1, Wolfgang H. Oertel3, Anders Björklund4, Olle Lindvall5,6 and Paola Piccini1

Cell therapy studies in patients with Parkinson’s disease (PD) have been confined to intrastriatal transplantation of dopamine-rich fetal mesencephalic tissue in efforts to improve motor performance. Although some PD patients receiving the dopamine-rich grafts showed improvements in motor symptoms due to replacement of dopaminergic neurons, they still suffered from nonmotor symptoms including depression, fatigue, visual hallucinations, and sleep problems. Using functional imaging and clinical evaluation of motor and nonmotor symptoms in three PD patients transplanted with intrastriatal fetal grafts 13 to 16 years previously, we assessed whether reestablishment of dopaminergic neuronal networks is sufficient to improve a broad range of symptoms. At 13 to 16 years after transplantation, dopaminergic innervation was restored to normal levels in basal ganglia and preserved in a number of extrabasal ganglia areas. These changes were associated with long-lasting relief of motor symptoms. Then, we assessed the integrity of their serotonergic and norepinephrine neuronal systems using [11C]DASB {[11C]3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile} positron emission tomography (PET) and 18F-dopa PET, respectively. 18F-Dopa uptake in the locus coeruleus was within the normal range. In contrast, [11C]DASB uptake in the raphe nuclei and regions receiving serotonergic projections was markedly reduced. These results indicate ongoing degeneration of serotonergic raphe nuclei and their projections to regions involved in the regulation of sleep, arousal, feeding, satiety, mood, and emotion. Our findings indicate that future cell-based therapies using fetal tissue or stem cells in PD patients may require additional grafts of serotonergic neurons to relieve nonmotor symptoms by restoring serotonergic neurotransmission in specific cerebral targets.