Lipidomic profiling in mouse brain reveals differences between ages and genders, with smaller changes associated with α-synuclein genotype

Advances in lipidomics technology have facilitated the precise detection, identification and profiling of lipid species within tissues. Mass spectrometry allows for identification of lipids as a function of the total number of carbons and double bonds in their acyl chains. Such detailed descriptions of lipid composition can provide a basis for further investigation of cell signaling and metabolic pathways, both physiological and pathological. Here, we applied phospholipid profiling to mouse models relevant to Parkinson's disease, using mice that were transgenic for human alpha-synuclein (alpha Syn) or deleted of endogenous alpha Syn. Proposed functions of alpha Syn include phospholipid binding, regulation of membrane composition, and regulation of vesicular pools. We investigated whether alpha Syn gene dosage interacts with differences in phospholipid composition across brain regions or with age-related changes in brain phospholipid composition. The most dramatic phospholipid changes were observed in alpha Syn wild-type animals as a function of age and gender. alpha Syn genotype-specific changes were also observed in aged, but not young, mice. Our results provide a detailed and systematic characterization of brain phospholipid composition in mice and identify age-related changes relevant both to Parkinson's disease and to normal aging.