title: Lipidomic profiling in mouse brain reveals differences between ages and genders, with smaller changes associated with alpha-synuclein genotype.
abstract: 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 (alphaSyn) or deleted of endogenous alphaSyn. Proposed functions of alphaSyn include phospholipid binding, regulation of membrane composition, and regulation of vesicular pools. We investigated whether alphaSyn 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 alphaSyn wild-type animals as a function of age and gender. alphaSyn 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.
authors.affiliation: Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Irit
authors.initials: I
authors.lastname: Rappley
authors.forename: David S
authors.initials: DS
authors.lastname: Myers
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Milne
authors.forename: Pavlina T
authors.initials: PT
authors.lastname: Ivanova
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lavoie
authors.forename: H Alex
authors.initials: HA
authors.lastname: Brown
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D020404:Glycerophospholipids / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D025341:Principal Component Analysis; D012737:Sex Factors; D051844:alpha-Synuclein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D020404:Glycerophospholipids; D051844:alpha-Synuclein