Computational Analysis of SOD1-G93A Mouse Muscle Biomarkers for Comprehensive Assessment of ALS Progression.

IF 4 2区 医学 Q1 CLINICAL NEUROLOGY
Pedro Gómez-Gálvez, Victoria Navarro, Ana M Castro, Carmen Paradas, Luis M Escudero
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引用次数: 0

Abstract

Aims: To identify potential image biomarkers of neuromuscular disease by analysing morphological and network-derived features in skeletal muscle biopsies from a murine model of amyotrophic lateral sclerosis (ALS), the SOD1G93A mouse and wild-type (WT) controls at distinct stages of disease progression.

Methods: Using the NDICIA computational framework, we quantitatively evaluated histological differences between skeletal muscle biopsies from SOD1G93A and WT mice. The process involved the selection of a subset of features revealing these differences. A subset of discriminative features was selected to characterise these differences, and their temporal dynamics were assessed across disease stages.

Results: Our findings demonstrate that muscle pathology in the mutant model evolves from early alterations in muscle fibre arrangement, detectable at the presymptomatic stage through graph theory features, to the subsequent development of the typical morphological pattern of neurogenic atrophy at more advanced disease stages.

Conclusions: Our assay identifies a neurogenic signature in mutant muscle biopsies, even when the disease is phenotypically imperceptible.

SOD1-G93A小鼠肌肉生物标志物综合评估ALS进展的计算分析
目的:通过分析肌萎缩性侧索硬化症(ALS)小鼠模型、SOD1G93A小鼠和野生型(WT)对照在不同疾病进展阶段的骨骼肌活检的形态学和网络衍生特征,识别神经肌肉疾病的潜在图像生物标志物。方法:使用NDICIA计算框架,我们定量评估SOD1G93A和WT小鼠骨骼肌活检的组织学差异。这个过程包括选择揭示这些差异的特征子集。选择一组判别特征来表征这些差异,并评估其在疾病阶段的时间动态。结果:我们的研究结果表明,突变模型中的肌肉病理从早期肌纤维排列的改变(在症状前阶段通过图论特征可检测到)演变为随后在更晚期的疾病阶段发展为典型的神经源性萎缩形态模式。结论:我们的分析在突变的肌肉活检中识别出神经源性特征,即使这种疾病在表型上难以察觉。
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来源期刊
CiteScore
8.20
自引率
2.00%
发文量
87
审稿时长
6-12 weeks
期刊介绍: Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.
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