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

Abstract

Abstract 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. Few studies on PD have focused on the lipid profile of cerebrospinal fluid (CSF), which may represent an ideal biomarker for disease diagnosis. Methods Here, 6-hydroxydopamine (6-OHDA) was used to construct a rat model of PD, and the lipid profile in 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), and free fatty acid (FFA), and 10 lipid species exhibited significantly altered profiles 2 weeks after 6-OHDA administration, and significant changes in eicosanoids, TG, CAR, and 3 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, 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. Conclusions These results revealed that nonprogressive nigrostriatal degeneration induced by 6-OHDA promotes the expression of an impairment-related lipidomic signature in CSF that may function as a biomarker to aid in PD diagnosis, and the level of eicosanoids, TG families and TG (16:0_20:0_18:1) in CSF may reveal pathological changes in the midbrain of PD patients.