Lipidomic analysis of p-chlorophenylalanine-treated mice using continuous-flow two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry

Abstract

Rationale: Although serotonin deficiency is involved with various physiological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia and depression, the serotonin-dependent pathomechanisms remain poorly understood, particularly from a lipidomics perspective.

Methods: This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipid profiling of p-chlorophenylalanine (pCPA)-treated, serotonin-deficient mice using continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry (NP/RP 2D LC/QTOFMS). Principal component analysis (PCA) was performed to distinguish significantly altered lipids between the pCPA-treated mice and control mice.

Results: Eighteen lipid biomarkers were associated with pCPA-induced serotonin deficiency. Specifically, lipid species of lysophosphatidylethanolamine (LPE), phosphatidylethanolamine (PE), sphingomyelin (SM), galactosylceramide (GalCer), glucotosylceramide (GluCer), lactosylceramide (LacCer) and triacylglycerol (TG) were down-regulated whereas glycerophosphocholine (PC) and phosphatidylinositol (PI) were up-regulated in the pCPA-treated mice compared with control mice.

Conclusions: This work demonstrates the significant effects of serotonin deficiency on lipid metabolisms and will facilitate improved understanding of pathomechanisms in serotonin deficiency, particularly from a lipidomics perspective.