Using MALDI-MSI in acute and subacute MPTP mice, the study reports time-dependent reductions of polyunsaturated phosphatidylcholines (e.g., PC 36:4, PC 38:6, PC 40:8) in motor cortex and striatum that correlate with dopaminergic neuron loss and motor deficits.

Pinpoints specific membrane lipid changes as potential PD biomarkers and implicates altered lipid metabolism/membrane integrity in disease progression, offering translational leads for biomarker development or lipid-targeted neuroprotective strategies.

Parkinson's disease (PD) is a neurodegenerative disorder caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Lipid metabolism, especially phospholipids, has been reported to be altered in PD. The purpose of this study is to investigate the temporal expression and spatial distribution of phospholipids in the motor cortex and striatum at different time points of PD using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model. Mice were injected with saline (NSS) or MPTP at two different time points to create acute and subacute models. Motor analysis was performed at 0, 3, 7, 14, and 21 days post-injection. Tyrosine hydroxylase (TH) staining revealed progressive damage of neurons in the substantia nigra compacta (SNc) and reduced striatal fibers in MPTP-treated animals. By using MALDI-MSI, we identified changes in phosphatidylcholine (PC) profiles in the brains of MPTP-treated animals. Polyunsaturated PCs, including PC 36:4 (16:0/20:4), PC 38:6 (16:0/22:6), and PC 40:8 (18:2/22:6), were decreased in the MPTP-treated groups. These reductions were time-dependent and were more pronounced in the subacute MPTP-treated group. The loss of dopamine neurons caused by MPTP may be associated with the selective loss of polyunsaturated PCs in brain membranes, indicating that lipid metabolism and membrane structural alterations may contribute to the pathology of PD.