Limbic Serotonergic Plasticity Contributes to the Compensation of Apathy in Early Parkinson's Disease
Limbic Serotonergic Plasticity Contributes to the Compensation of Apathy in Early Parkinson's Disease
复制标题
边缘系统5-羟色胺可塑性对早期帕金森病冷漠的补偿作用
DOI：
10.1002/mds.28971
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发表时间：
2022-03-03
影响因子：
8.6
通讯作者：
Thobois, Stephane
中科院分区：
文献类型：
--
作者：
Prange, Stephane;Metereau, Elise;Thobois, Stephane
背景伴有冷漠的原发性帕金森病（PD）患者表现出明显的边缘系统血清素能功能障碍和微结构混乱。这种独特的病变轮廓在诊断时是否需要不同的预后仍然未知。目的探讨帕金森病（PD）患者在诊断时是否存在情感淡漠，其多巴胺能和多巴胺能功能障碍的进展及其与运动和非运动功能损害的关系。方法采用双示踪剂正电子发射断层扫描纵向队列研究，对13例原发性冷漠型和13例非冷漠型PD患者进行研究。我们在基线和3 - 5年后使用[C-11] PE 2 I用于多巴胺转运蛋白和[C-11]DASB用于5-羟色胺转运蛋白定量突触前多巴胺能和多巴胺能病理学的进展，使用线性混合效应模型和中介分析比较临床损害和基于感兴趣区域分析的组间纵向演变。结果在多巴胺替代治疗开始后，在随访时，诊断时有冷漠的患者（n = 10）的冷漠、抑郁和焦虑改善至无冷漠的患者（n = 11）的水平。两组患者的运动障碍进展相似，而两组患者均出现轻度冲动行为。两组纹状体苍白球和中脑皮质边缘突触前多巴胺能损失的进展相似，壳核，尾状核和苍白球的多巴胺能病理学也相似。相反，在冷漠患者的腹侧纹状体和前扣带皮层中，多巴胺能神经支配选择性增加，除了多巴胺替代疗法外，还有助于冷漠的逆转。结论诊断时情感淡漠的患者在诊断后5年内表现出边缘系统多巴胺能神经支配的代偿性变化，多巴胺能神经可塑性有助于情感淡漠的逆转。多巴胺能可塑性和多巴胺能治疗之间的关系需要进一步的纵向研究。(c)2022国际帕金森和运动障碍协会
Background De novo Parkinson's disease (PD) patients with apathy exhibit prominent limbic serotonergic dysfunction and microstructural disarray. Whether this distinctive lesion profile at diagnosis entails different prognosis remains unknown. Objectives To investigate the progression of dopaminergic and serotonergic dysfunction and their relation to motor and nonmotor impairment in PD patients with or without apathy at diagnosis. Methods Thirteen de novo apathetic and 13 nonapathetic PD patients were recruited in a longitudinal double-tracer positron emission tomography cohort study. We quantified the progression of presynaptic dopaminergic and serotonergic pathology using [C-11]PE2I for dopamine transporter and [C-11]DASB for serotonin transporter at baseline and 3 to 5 years later, using linear mixed-effect models and mediation analysis to compare the longitudinal evolution between groups for clinical impairment and region-of-interest-based analysis. Results After the initiation of dopamine replacement therapy, apathy, depression, and anxiety improved at follow-up in patients with apathy at diagnosis (n = 10) to the level of patients without apathy (n = 11). Patients had similar progression of motor impairment, whereas mild impulsive behaviors developed in both groups. Striato-pallidal and mesocorticolimbic presynaptic dopaminergic loss progressed similarly in both groups, as did serotonergic pathology in the putamen, caudate nucleus, and pallidum. Contrastingly, serotonergic innervation selectively increased in the ventral striatum and anterior cingulate cortex in apathetic patients, contributing to the reversal of apathy besides dopamine replacement therapy. Conclusion Patients suffering from apathy at diagnosis exhibit compensatory changes in limbic serotonergic innervation within 5 years of diagnosis, with promising evidence that serotonergic plasticity contributes to the reversal of apathy. The relationship between serotonergic plasticity and dopaminergic treatments warrants further longitudinal investigations. (c) 2022 International Parkinson and Movement Disorder Society