Transcriptional specialization shapes abnormal cortical morphological similarity gradients in Wilson’s disease

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-08-16 DOI:10.1016/j.brainres.2025.149887

Yuqi Song , Weiqi Wang , Sheng Hu , Yulong Yang , Chuanfu Li , Kou Xu , Zilong Li , Taohua Wei , Wenming Yang

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Abstract

Background

Neuroimaging studies have revealed structural abnormalities in the brains of individuals with Wilson’s disease (WD), particularly within the basal ganglia, and the associated molecular mechanisms have been elucidated. However, the structural damage in the cerebral cortex, along with its underlying biological and molecular processes, remains elusive. Here, we investigated the abnormalities in cortical morphological similarity gradients associated with WD and further unraveled their underlying transcriptional specialization.

Methods

First, we analyzed cortical morphological features from structural magnetic resonance imaging scans from 102 WD patients and 90 healthy controls (HCs) and then computed the cortical morphological similarity (MS) connections. Subsequently, the diffusion map embedding approach was employed to investigate the cortical MS gradients. Finally, the differences in MS gradients between WD and HC were analyzed and their underlying clinical relevance and transcriptional specialization were revealed using clinical symptoms and gene expression data, respectively.

Results

Compared with HC, WD patients exhibited regional differences across extensive brain networks in both the first and second MS gradients. Alterations in MS gradient alterations correlated with age, neurological symptoms, liver function symptoms, and motor-related processing. Partial least squares (PLS) regression analysis results indicated a significant association between MS gradients and gene expression profiles (PLS components). Gene enrichment analysis showed that the transcriptional specialization of PLS components was enriched in biological processes such as cell projection organization, regulation of protein organization, and GPTase-mediated signal transduction, all of which are relevant to WD. The transcriptional specializations influencing the MS gradient of WD were also enriched in WD’s pathological genes associated with WD and other neuropsychiatric risks, such as dystonia and Parkinsonism.

Conclusion

Overall, this research offers new perspectives on the neurobiological foundations that govern the emergence of complex neural architectures and associated mental manifestations in WD.

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在Wilson病中，转录特化形成异常的皮质形态相似性梯度

神经影像学研究已经揭示了威尔逊氏病（WD）患者的大脑结构异常，特别是在基底神经节内，相关的分子机制已经阐明。然而，大脑皮层的结构损伤及其潜在的生物和分子过程仍然难以捉摸。在这里，我们研究了与WD相关的皮质形态相似性梯度的异常，并进一步揭示了它们潜在的转录特化。方法首先分析102例WD患者和90例健康对照（hc）脑皮层结构磁共振成像（mri）的形态学特征，计算脑皮层形态相似连接（MS）。随后，采用扩散图嵌入方法研究皮质质谱梯度。最后，分析了WD和HC之间MS梯度的差异，并分别通过临床症状和基因表达数据揭示了其潜在的临床相关性和转录专门化。结果与HC相比，WD患者在第一和第二MS梯度中表现出广泛的脑网络区域差异。MS梯度改变的改变与年龄、神经症状、肝功能症状和运动相关加工相关。偏最小二乘（PLS）回归分析结果表明，MS梯度与基因表达谱（PLS成分）之间存在显著相关性。基因富集分析表明，PLS组分的转录特化富集在细胞投射组织、蛋白组织调控、gpase介导的信号转导等生物过程中，均与WD相关。影响WD MS梯度的转录专一化还富集于与WD和其他神经精神风险（如肌张力障碍和帕金森病）相关的WD病理基因。总的来说，本研究为控制WD中复杂神经结构和相关精神表现的神经生物学基础提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.