帕金森病小鼠模型纹状体代谢组学改变：液相色谱-质谱综合分析

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-08-22 DOI:10.1016/j.ibneur.2025.08.017

Zhiqiang Wu , Jing Dai , Bo Lv, Cunjin Su, Delai Xu

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引用次数: 0

摘要

目的帕金森病（PD）是一种慢性神经退行性疾病，其病理特征是黑质致密部多巴胺能神经元的进行性丧失，导致纹状体多巴胺水平显著下降。本研究旨在系统分析帕金森病不同阶段纹状体代谢物的变化，以识别潜在的生物标志物，阐明病理机制，探索治疗靶点。方法将72只小鼠分为6组，包括1个对照组和5个PD模型组（w1 ~ w5，根据1-甲基-4-苯基-1,2,3,6-四氢吡啶/probenecid诱导时间分为不同阶段）。全面采集纹状体组织，利用代谢组学技术检测小分子代谢物。通过正交偏最小二乘判别分析（OPLS-DA）的投影值和LASSO有序逻辑回归的系数值，筛选潜在的差异代谢物生物标志物。结果鉴定出13种潜在的差异代谢物，包括麦角钙化醇、戊二酸、依替弗林和鸟嘌呤等。途径富集分析显示，嘌呤代谢是受干扰最显著的途径。此外，受试者工作特征曲线分析表明，由这13种代谢物组成的生物标志物面板可以有效区分PD的不同阶段。结论纹状体在帕金森病的不同阶段表现出不同的代谢特征，其中嘌呤代谢变化最为明显。本研究发现的特征性代谢物和代谢途径有助于阐明PD的病理生理特征，并可能指导精准治疗。

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Striatal metabolomic alterations in a mouse model of Parkinson's disease: A comprehensive liquid chromatography-mass spectrometry analysis

Objective

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized pathologically by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a significant decline in striatal dopamine levels. This study aims to systematically analyze alterations in striatal metabolites across different stages of PD to identify potential biomarkers, elucidate pathological mechanisms, and explore therapeutic targets.

Methods

A total of 72 mice were divided into six groups, including one control group and five PD model groups (W1–W5, representing distinct stages based on the duration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid induction). Striatal tissues were comprehensively collected, and small-molecule metabolites were detected using metabolomics techniques. Potential differential metabolite biomarkers were screened through variable importance in projection values from orthogonal partial least squares-discriminant analysis (OPLS-DA) and coefficient values from LASSO ordinal logistic regression.

Results

Thirteen potential differential metabolites were identified, including Ergocalciferol, Glutaric acid, Etilefrine, and Guanine, among others. Pathway enrichment analysis revealed that purine metabolism emerged as the most significantly perturbed pathway. Additionally, receiver operating characteristic curve analysis demonstrated that the biomarker panel composed of these 13 metabolites effectively distinguished different stages of PD.

Conclusion

The striatum exhibits distinct metabolic profiles at different stages of PD, with purine metabolism showing the most pronounced alterations. The characteristic metabolites and metabolic pathways identified in this study contribute to elucidating the pathophysiological features of PD and may guide precision therapy.

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