Assessing Neurometabolic Alterations, Glutathione Depletion and Iron Deposition in the Mesostriatal Pathway of Parkinson's Disease

Motivation: Emerging insights into the pathophysiology of Parkinson's disease (PD) underscore the involvement of dysregulated neurotransmission, iron accumulation and oxidative stress. Goal(s): Our aim is to explore the interactions among the excitatory and inhibitory neurometabolites, the antioxidant glutathione (GSH), and magnetic susceptibility in PD. Approach: Spectra-editing of Γ-aminobutyric acid (GABA), GSH and quantitative susceptibility mapping were simultaneously employed to reveal disease-specific alterations in the mesostriatal pathway in PD. Results: PD demonstrated metabolic dysregulation in the nigro-striatal circuits, characterized by a concomitant reduction in GABA and GSH levels, accompanied with iron deposition. Impact: These findings offer valuable insights into the pathophysiology of PD and may inform future therapeutic strategies targeting metabolic and oxidative stress pathways.