Lipidomic Profiling in Mouse Brain Reveals Differences Between Ages and Genders, with Smaller Changes Associated with Alpha-synuclein Genotype

Overview

Journal J Neurochem

Specialties Chemistry
Neurology

Date 2009 Jul 25

PMID 19627450

Citations 42

Authors

Irit Rappley

David S Myers

Stephen B Milne

Pavlina T Ivanova

Matthew J LaVoie

H Alex Brown

Dennis J Selkoe

Affiliations

Soon will be listed here.

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.

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References

Young R, Holowka D, Baird B . A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation. J Biol Chem. 2003; 278(23):20746-52. DOI: 10.1074/jbc.M211402200. View

Larsen K, Schmitz Y, Troyer M, Mosharov E, Dietrich P, Quazi A . Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci. 2006; 26(46):11915-22. PMC: 6674868. DOI: 10.1523/JNEUROSCI.3821-06.2006. View

Lyons K, Hubble J, Troster A, Pahwa R, Koller W . Gender differences in Parkinson's disease. Clin Neuropharmacol. 1998; 21(2):118-21. View

Lavedan C . The synuclein family. Genome Res. 1998; 8(9):871-80. DOI: 10.1101/gr.8.9.871. View

Tofaris G, Spillantini M . Alpha-synuclein dysfunction in Lewy body diseases. Mov Disord. 2005; 20 Suppl 12:S37-44. DOI: 10.1002/mds.20538. View

Jo E, McLaurin J, Yip C, St George-Hyslop P, Fraser P . alpha-Synuclein membrane interactions and lipid specificity. J Biol Chem. 2000; 275(44):34328-34. DOI: 10.1074/jbc.M004345200. View

Litvan I, Chesselet M, Gasser T, Di Monte D, Parker Jr D, Hagg T . The etiopathogenesis of Parkinson disease and suggestions for future research. Part II. J Neuropathol Exp Neurol. 2007; 66(5):329-36. DOI: 10.1097/nen.0b013e318053716a. View

Ellis C, Murphy E, Mitchell D, Golovko M, Scaglia F, Barcelo-Coblijn G . Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol. 2005; 25(22):10190-201. PMC: 1280279. DOI: 10.1128/MCB.25.22.10190-10201.2005. View

Roberts L, McCombie G, Titman C, Griffin J . A matter of fat: an introduction to lipidomic profiling methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2008; 871(2):174-81. DOI: 10.1016/j.jchromb.2008.04.002. View

10.

Adibhatla R, Hatcher J, Dempsey R . Lipids and lipidomics in brain injury and diseases. AAPS J. 2006; 8(2):E314-21. PMC: 3231558. DOI: 10.1007/BF02854902. View

11.

Zeng X, Zheng X, Xiang Y, Cho H, Jessen J, Zhong T . Phospholipase D1 is required for angiogenesis of intersegmental blood vessels in zebrafish. Dev Biol. 2009; 328(2):363-76. PMC: 2688691. DOI: 10.1016/j.ydbio.2009.01.035. View

12.

Rouzer C, Ivanova P, Byrne M, Milne S, Marnett L, Brown H . Lipid profiling reveals arachidonate deficiency in RAW264.7 cells: Structural and functional implications. Biochemistry. 2006; 45(49):14795-808. PMC: 2443946. DOI: 10.1021/bi061723j. View

13.

Tofaris G, Spillantini M . Physiological and pathological properties of alpha-synuclein. Cell Mol Life Sci. 2007; 64(17):2194-201. PMC: 11135986. DOI: 10.1007/s00018-007-7217-5. View

14.

Golovko M, Rosenberger T, Feddersen S, Faergeman N, Murphy E . Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids. J Neurochem. 2007; 101(1):201-11. DOI: 10.1111/j.1471-4159.2006.04357.x. View

15.

Assayag K, Yakunin E, Loeb V, Selkoe D, Sharon R . Polyunsaturated fatty acids induce alpha-synuclein-related pathogenic changes in neuronal cells. Am J Pathol. 2007; 171(6):2000-11. PMC: 2111122. DOI: 10.2353/ajpath.2007.070373. View

16.

Ivanova P, Milne S, Byrne M, Xiang Y, Brown H . Glycerophospholipid identification and quantitation by electrospray ionization mass spectrometry. Methods Enzymol. 2007; 432:21-57. DOI: 10.1016/S0076-6879(07)32002-8. View

17.

Van Den Eeden S, Tanner C, Bernstein A, Fross R, Leimpeter A, Bloch D . Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003; 157(11):1015-22. DOI: 10.1093/aje/kwg068. View

18.

Han X, Abendschein D, Kelley J, Gross R . Diabetes-induced changes in specific lipid molecular species in rat myocardium. Biochem J. 2000; 352 Pt 1:79-89. PMC: 1221434. View

19.

Spillantini M, Schmidt M, Lee V, Trojanowski J, Jakes R, Goedert M . Alpha-synuclein in Lewy bodies. Nature. 1997; 388(6645):839-40. DOI: 10.1038/42166. View

20.

Barcelo-Coblijn G, Golovko M, Weinhofer I, Berger J, Murphy E . Brain neutral lipids mass is increased in alpha-synuclein gene-ablated mice. J Neurochem. 2007; 101(1):132-41. DOI: 10.1111/j.1471-4159.2006.04348.x. View