Bu Shuting, Li Xiaolu, Pang Huize, Zhao Mengwan, Wang Juzhou, Liu Yu, Yu Hongmei, Jiang Yueluan, Fan Guoguang
Departments of Radiology, The First Hospital of China Medical University, Shenyang 110001, China.
Neurology, The First Hospital of China Medical University, Shenyang 110001, China.
J Neurosci. 2025 Feb 12;45(7):e1492242024. doi: 10.1523/JNEUROSCI.1492-24.2024.
Hierarchy has been identified as a principle underlying the organization of human brain networks. However, it remains unclear how the network hierarchy is disrupted in Parkinson's disease (PD) motor symptoms and how it is modulated by the underlying genetic architecture. The aim of this study was to explore alterations in the motor functional hierarchical organization of the cerebrum and their underlying genetic mechanism. In this study, the brain network hierarchy of each group was described through a connectome gradient analysis among 68 healthy controls (HC), 70 postural instability and gait difficulty (PIGD) subtype, and 69 tremor-dominant (TD) subtype, including both male and female participants, according to its motor symptoms. Furthermore, transcription-neuroimaging association analyses using gene expression data from Allen Human Brain Atlas and case-control gradient differences were performed to identify genes associated with gradient alterations. Different PD motor subtypes exhibited contracted principal and secondary functional gradients relative to HC. The identified genes in different PD motor subtypes enriched for shared biological processes like metal ion transport and inorganic ion transmembrane transport. In addition, these genes were overexpressed in Ntsr+ neurons cell, enriched in extensive cortical regions and wide developmental time windows. Aberrant cerebral functional gradients in PD-related motor symptoms have been detected, and the motor-disturbed genes have shared biological functions. The present findings may contribute to a more comprehensive understanding of the molecular mechanisms underlying hierarchical alterations in PD.
层级结构已被确定为人类大脑网络组织的一个基本原则。然而，目前尚不清楚帕金森病（PD）运动症状中网络层级结构是如何被破坏的，以及它是如何受到潜在遗传结构调节的。本研究的目的是探索大脑运动功能层级组织的改变及其潜在的遗传机制。在本研究中，根据运动症状，通过对68名健康对照者（HC）、70名姿势不稳和步态障碍（PIGD）亚型患者以及69名震颤为主（TD）亚型患者（包括男性和女性参与者）进行连接组梯度分析，描述了每组的脑网络层级结构。此外，利用来自艾伦人类大脑图谱的基因表达数据进行转录-神经影像关联分析，并进行病例对照梯度差异分析，以确定与梯度改变相关的基因。相对于HC，不同的PD运动亚型表现出收缩的主要和次要功能梯度。在不同的PD运动亚型中鉴定出的基因富集于共同的生物学过程，如金属离子转运和无机离子跨膜转运。此外，这些基因在Ntsr+神经元细胞中过表达，在广泛的皮质区域和广泛的发育时间窗口中富集。已检测到与PD相关运动症状异常的脑功能梯度，且运动障碍相关基因具有共同的生物学功能。本研究结果可能有助于更全面地理解PD层级改变背后的分子机制。
