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.