BackgroundParkinson’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.MethodsHere, 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.ResultsEstablishment 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.ConclusionThese 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.
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.
Background: Abnormal accumulation of lipids is found in dopamine neurons and resident microglia in the substantia nigra of patients with Parkinson’s disease (PD). The accumulation of lipids is an important risk factor for PD. Previous studies have mainly focussed on lipid metabolism in peripheral blood, but little attention has been given to cerebrospinal fluid (CSF). We drew the lipidomic signature in CSF from PD patients and evaluated the role of lipids in CSF as biomarkers for PD diagnosis. Methods: Based on lipidomic approaches, we investigated and compared lipid metabolism in CSF from PD patients and healthy controls without dyslipidaemia in peripheral blood and explored the relationship of lipids between CSF and serum by Pearson correlation analysis. Results: A total of 231 lipid species were detected and classified into 13 families in the CSF. The lipid families, including phosphatidylcholine (PC), sphingomyelin (SM) and cholesterol ester (CE), had significantly increased expression compared with the control. Hierarchical clustering was performed to distinguish PD patients based on the significantly changed expression of 34 lipid species. Unsupervised and supervised methods were used to refine this classification. A total of 12 lipid species, including 3-hydroxy-dodecanoyl-carnitine, Cer(d18:1/24:1), CE(20:4), CE(22:6), PC(14:0/18:2), PC(O-18:3/20:2), PC(O-20:2/24:3), SM(d18:0/16:0), SM(d18:2/14:0), SM(d18:2/24:1), SM(d18:1/20:1) and SM(d18:1/12:0), were selected to draw the lipidomic signature of PD. Correlation analysis was performed and showed that the CE family and CE (22:6) in CSF had a positive association with total cholesterol in the peripheral blood from PD patients but not from healthy controls. Conclusions: Our results revealed that the lipidomic signature in CSF may be considered a potential biomarker for PD diagnosis, and increased CE, PC and SM in CSF may reveal pathological changes in PD patients, such as blood–brain barrier leakage.
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