H. Alex Brown
Principle Investigator; Professor of Pharmacology, Chemistry, and Biochemistry; Associate Director, VICB;
Last active: 2/12/2015

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

Rappley I, Myers DS, Milne SB, Ivanova PT, Lavoie MJ, Brown HA, Selkoe DJ
J Neurochem. 2009 111 (1): 15-25

PMID: 19627450 · PMCID: PMC2752313 · DOI:10.1111/j.1471-4159.2009.06290.x

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.

MeSH Terms (17)

Age Factors alpha-Synuclein Analysis of Variance Animals Brain Female Gene Dosage Glycerophospholipids Humans Male Mass Spectrometry Metabolome Mice Mice, Inbred DBA Mice, Transgenic Principal Component Analysis Sex Factors

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