Transcriptomic and neurotransmitter correlates of structure and function spatial variations patterns in spinocerebellar Ataxia

IF 6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2026-01-01 Epub Date: 2025-12-18 DOI:10.1016/j.nbd.2025.107228

Manxi Xu , Yuanhao Li , Jixin Luan , Aocai Yang , Li Zhu , Ni Shu , Gaoxiang Ouyang , Yunjing Xue , Linwei Zhang , Guolin Ma

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引用次数: 0

Abstract

Background

Spinocerebellar ataxia (SCA) is characterized by cortical structural and functional impairments, but the underlying biological mechanisms remain poorly understood.

Methods

We applied T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI (fMRI) to investigate cortical alterations in 49 SCA patients and 48 matched controls. Cortical thickness and amplitude of low-frequency fluctuations (ALFF) were quantified and compared with spatial maps of 19 neurotransmitter systems. Gene expression patterns were examined using partial least squares regression, followed by gene ontology analysis to identify associated biological processes.

Results

Both cortical thickness and ALFF emerged as sensitive biomarkers of cortical impairment in SCA. Thickness alterations were strongly associated with disruptions in cholinergic, serotonergic, and glutamatergic systems. ALFF alterations were linked to toxin-response and detoxification processes, with relevant gene expression enriched in astrocytes.

Conclusion

Our convergent imaging–transcriptomic analysis integrates direct molecular vulnerability and CTC-based transsynaptic degeneration, yielding a unified systems-level view of SCA. These findings go beyond correlation by prioritizing molecular pathways and non-neuronal cellular targets and enabling network-informed prediction of additional vulnerable regions.

Abstract Image

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脊髓小脑性共济失调的结构和功能空间变化模式的转录组学和神经递质相关性。

背景：脊髓小脑性共济失调（SCA）以皮质结构和功能损伤为特征，但其潜在的生物学机制尚不清楚。方法：应用t1加权磁共振成像（MRI）和静息状态功能磁共振成像（fMRI）研究49例SCA患者和48例匹配对照的皮质改变。量化皮层厚度和低频波动幅度（ALFF），并与19个神经递质系统的空间图进行比较。利用偏最小二乘回归分析基因表达模式，然后通过基因本体分析来识别相关的生物过程。结果：皮质厚度和ALFF是SCA患者皮质损伤的敏感生物标志物。厚度改变与胆碱能、血清素能和谷氨酸能系统的破坏密切相关。ALFF的改变与毒素反应和解毒过程有关，相关基因在星形胶质细胞中表达丰富。结论：我们的聚合成像-转录组学分析整合了直接的分子易感性和基于ctc的跨突触变性，产生了统一的SCA系统级视图。这些发现超越了分子途径和非神经元细胞目标的优先级相关性，并实现了对其他脆弱区域的网络信息预测。

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

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.