Department of Neurology, Zhongnan Hospital, Wuhan University, No.169, Donghu Road, Wuhan, Hubei 430071, China.
Department of Neurology, Zhongnan Hospital, Wuhan University, No.169, Donghu Road, Wuhan, Hubei 430071, China.
J Stroke Cerebrovasc Dis. 2024 Oct;33(10):107921. doi: 10.1016/j.jstrokecerebrovasdis.2024.107921. Epub 2024 Aug 11.
Depressive symptoms are a common concomitant of cerebral small vessel disease (CSVD), of which pathogenesis requires more study. White matter microstructural abnormalities and proteomic alternation have been widely reported regarding depression in the elderly with CSVD. Exploring the relationship between cerebral white matter microstructural alterations and serum proteins may complete the explanation of molecular mechanisms for the findings from neuroimaging research of CSVD combined with depressive symptoms.
An untargeted proteomics approach based on mass spectrometry was used to obtain serum proteomic profiles, which were clustered into co-expression protein modules. White matter microstructural integrity was measured using the FMRIB Software Library (FSL) and MATLAB to analyze diffusion tensor imaging (DTI) data and calculate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for 50 regions of interest (ROI). Integrating the proteome with the DTI results, weighted gene co-expression analysis (WGCNA) was used to identify protein modules related to white matter microstructural alterations, and the proteins of the corresponding modules were analyzed for functional enrichment through bioinformatics techniques.
DTI measurements were analCerebral small vessel disease (CSVD); Depression; Diffusion tensor imaging (DTI); Proteomics; Inflammationyzed between individuals with CSVD and depressive symptoms (CSVD+D) (n = 24) and those without depressive symptoms (CSVD-D) (n = 35). Results showed an overall increase in MD, AD, and RD within the left hemisphere of the CSVD+D group, suggesting widespread loss of white matter integrity and axonal demyelination, including left superior longitudinal fasciculus (SLF), left posterior corona radiata (PCR) and right external capsule (EC). We identified two protein modules associated with DTI diffusivity, and functional enrichment analyses revealed that complement and coagulation cascades and immune responses participate in the alternation of white matter microstructure in the CSVD+D group.
The results suggested immune- and inflammation-related mechanism was associated with white matter microstructure changes in CSVD with depressive symptoms.
抑郁症状是脑小血管病（CSVD）的常见伴随症状，其发病机制尚需进一步研究。已有研究广泛报道，脑小血管病伴发抑郁的老年人存在白质微结构异常和蛋白质组改变。探索脑白质微结构改变与血清蛋白之间的关系，可能有助于完善 CSVD 合并抑郁症状的神经影像学研究结果的分子机制解释。
采用基于质谱的非靶向蛋白质组学方法获取血清蛋白质组谱，将其聚类为共表达蛋白模块。采用 FMRIB 软件库（FSL）和 MATLAB 分析弥散张量成像（DTI）数据，计算 50 个感兴趣区（ROI）的各向异性分数（FA）、平均弥散度（MD）、轴向弥散度（AD）和径向弥散度（RD）的差异，以测量脑白质微结构的完整性。将蛋白质组与 DTI 结果整合，采用加权基因共表达网络分析（WGCNA）鉴定与脑白质微结构改变相关的蛋白质模块，并通过生物信息学技术分析相应模块的蛋白质进行功能富集。
对 CSVD 伴抑郁（CSVD+D）（n=24）和无抑郁（CSVD-D）（n=35）患者的 DTI 测量结果进行分析。结果显示，CSVD+D 组左侧大脑半球 MD、AD 和 RD 整体升高，提示广泛的白质完整性丧失和轴突脱髓鞘，包括左侧上纵束（SLF）、左侧后冠状辐射（PCR）和右侧外囊（EC）。我们鉴定出与 DTI 弥散性相关的两个蛋白质模块，功能富集分析表明，补体和凝血级联反应以及免疫反应参与 CSVD+D 组白质微结构的改变。
结果提示，免疫和炎症相关机制与伴有抑郁症状的 CSVD 患者的白质微结构变化有关。
