Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.
Neurobiol Aging. 2019 Mar;75:83-97. doi: 10.1016/j.neurobiolaging.2018.11.013. Epub 2018 Nov 22.
In Parkinson's disease (PD), iron accumulation in the substantia nigra (SN) exacerbates oxidative stress and α-synuclein aggregation, leading to neuronal death. However, the influence of iron-related nigral degeneration on the subcortical function and global network configuration in PD remains unknown. Ninety PD patients and 38 normal controls underwent clinical assessments and multimodality magnetic resonance imaging scans. Iron accumulation in the inferior SN and disrupted functional connectivity between the bilateral striatums were observed in PD, and negative correlation between them was found in the whole population. The binarized functional network exhibited enhanced global efficiency and reduced local efficiency while the weighted functional network exhibited reduction in both, and both changes were correlated with nigral iron accumulation in PD. Mediation analysis demonstrated that the functional connectivity between bilateral striatums was a mediator between the nigral iron accumulation and weighted functional network alterations. In conclusion, our findings reveal that iron-related nigral degeneration possibly influences the functional topology mediated by striatal dysfunction, which extends the scientific understanding of PD pathogenesis.
在帕金森病（PD）中，铁在黑质（SN）中的积累加剧了氧化应激和α-突触核蛋白聚集，导致神经元死亡。然而，铁相关的黑质变性对 PD 患者的皮质下功能和全局网络结构的影响尚不清楚。90 名 PD 患者和 38 名正常对照者接受了临床评估和多模态磁共振成像扫描。在 PD 患者中观察到 SN 下部铁的积累和双侧纹状体之间的功能连接中断，并且在整个人群中发现了它们之间的负相关。二值化功能网络表现出增强的全局效率和降低的局部效率，而加权功能网络则表现出两者的降低，并且这些变化与 PD 中的黑质铁积累相关。中介分析表明，双侧纹状体之间的功能连接是黑质铁积累与加权功能网络改变之间的中介。总之，我们的发现表明，铁相关的黑质变性可能会影响由纹状体功能障碍介导的功能拓扑，这扩展了对 PD 发病机制的科学认识。
