Lipid profiles in the cerebrospinal fluid of rats with 6-hydroxydopamine-induced lesions as a model of Parkinson's disease.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with characteristic pathological abnormalities, including the loss of dopaminergic (DA) neurons, a dopamine-depleted striatum, and microglial activation. Lipid accumulation exhibits a close relationship with these pathologies in PD. Methods: Here, 6-hydroxydopamine (6-OHDA) was used to construct a rat model of PD, and the lipid profile in cerebrospinal fluid (CSF) obtained from model rats was analyzed using lipidomic approaches. Results: Establishment of this PD model was confirmed by apomorphine-induced rotation behaviors, loss of DA neurons, depletion of dopamine in the striatum, and microglial activation after 6-OHDA-induced lesion generation. Unsupervised and supervised methods were employed for lipid analysis. A total of 172 lipid species were identified in CSF and subsequently classified into 18 lipid families. Lipid families, including eicosanoids, triglyceride (TG), cholesterol ester (CE), and free fatty acid (FFA), and 11 lipid species exhibited significantly altered profiles 2 weeks after 6-OHDA administration, and significant changes in eicosanoids, TG, CE, CAR, and three lipid species were noted 5 weeks after 6-OHDA administration. During the period of 6-OHDA-induced lesion formation, the lipid families and species showed concentration fluctuations related to the recovery of behavior and nigrostriatal abnormalities. Correlation analysis showed that the levels of eicosanoids, CE, TG families, and TG (16:0_20:0_18:1) exhibited positive relationships with apomorphine-induced rotation behaviors and negative relationships with tyrosine hydroxylase (TH) expression in the midbrain. Conclusion: These results revealed that non-progressive nigrostriatal degeneration induced by 6-OHDA promotes the expression of an impairment-related lipidomic signature in CSF, and the level of eicosanoids, CE, TG families, and TG (16:0_20:0_18:1) in CSF may reveal pathological changes in the midbrain after 6-OHDA insult.