Spatial Multi-Omics Reveals Region-Specific Molecular Signatures in a 6-OHDA Model of Parkinson’s Disease

ABSTRACT: Parkinson’s disease (PD) is characterized by complex molecular and circuit-level alterations that extend beyond dopaminergic neurodegeneration, yet the spatial integration of metabolic and proteomic changes remains insufficiently explored. Here, we combined time-of-flight secondary ion mass spectrometry–based metabolite imaging with laser cell sorting proteomics to interrogate molecular alterations in the substantia nigra and striatum of the 6-hydroxydopamine toxin model of PD. Our analyses revealed distinct region-specific metabolic and proteomic signatures within primary lesion sites, and additionally uncovered unexpected and widespread off-target changes across neural circuits. These findings demonstrate that even in a toxin-induced model, PD pathology involves extensive reorganization of molecular networks and circuit-level processes, underscoring the complexity and diffuseness of disease mechanisms. By applying a spatially resolved, multilayered approach, this study expands the pathophysiological understanding of PD and provides a foundation for future investigations into the spatial and temporal dynamics of neurodegenerative disease progression.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Parkinson's Disease

SUBMITTER: Sun Young Lee  

LAB HEAD: Jin Gyeong

PROVIDER: PXD071834 | Pride | 2026-09-28

REPOSITORIES: Pride