title: Brain gangliosides of a transgenic mouse model of Alzheimer's disease with deficiency in GD3-synthase: expression of elevated levels of a cholinergic-specific ganglioside, GT1aα.
abstract: In order to examine the potential involvement of gangliosides in AD (Alzheimer's disease), we compared the ganglioside compositions of the brains of a double-transgenic (Tg) mouse model [APP (amyloid precursor protein)/PSEN1 (presenilin)] of AD and a triple mutant mouse model with an additional deletion of the GD3S (GD3-synthase) gene (APP/PSEN1/GD3S(-/-)). These animals were chosen since it was previously reported that APP/PSEN1/GD3S(-/-) triple-mutant mice performed as well as WT (wild-type) control and GD3S(-/-) mice on a number of reference memory tasks. Cholinergic neuron-specific gangliosides, such as GT1aα and GQ1bα, were elevated in the brains of double-Tg mice (APP/PSEN1), as compared with those of WT mice. Remarkably, in the triple mutant mouse brains (APP/PSEN1/GD3S(-/-)), the concentration of GT1aα was elevated and as expected there was no expression of GQ1bα. On the other hand, the level of c-series gangliosides, including GT3, was significantly reduced in the double-Tg mouse brain as compared with the WT. Thus, the disruption of the gene of a specific ganglioside-synthase, GD3S, altered the expression of cholinergic neuron-specific gangliosides. Our data thus suggest the intriguing possibility that the elevated cholinergic-specific ganglioside, GT1aα, in the triple mutant mouse brains (APP/PSEN1/GD3S(-/-)) may contribute to the memory retention in these mice.
authors.affiliation: Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ariga
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Itokazu
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDonald
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Susumu
authors.initials: S
authors.lastname: Ando
authors.forename: Robert K
authors.initials: RK
authors.lastname: Yu
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D059329:Cholinergic Neurons / Q000378:metabolism*; D004195:Disease Models, Animal; D005732:Gangliosides / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D012799:Sialyltransferases / Q000172:deficiency*
chemical_list: D016564:Amyloid beta-Protein Precursor; D000954:Antigens, Surface; D005732:Gangliosides; C508853:PSEN1 protein, human; D053764:Presenilin-1; C038777:chol-1 antigen; C062875:ganglioside A2B5; C084318:GT1aalpha ganglioside; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
references.citation: J Biol Chem. 1992 Jun 25;267(18):12632-8
references.pmid: 1618769
references.citation: J Neurochem. 2011 Mar;116(5):806-12
references.pmid: 21214549
references.citation: Biochemistry. 1988 Jan 12;27(1):52-8
references.pmid: 3349045
references.citation: J Biol Chem. 2001 Nov 30;276(48):44396-404
references.pmid: 11574545
references.citation: J Lipid Res. 1985 May;26(5):638-41
references.pmid: 2991403
references.citation: Neurochem Res. 2012 Jun;37(6):1230-44
references.pmid: 22410735
references.citation: Neurosci Lett. 1992 Feb 17;136(1):91-4
references.pmid: 1321969
references.citation: Neurobiol Aging. 2009 Nov;30(11):1777-91
references.pmid: 18258340
references.citation: Exp Brain Res. 1988;72(1):71-82
references.pmid: 3169197
references.citation: Neuroreport. 2009 Aug 5;20(12):1043-6
references.pmid: 19590389
references.citation: Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913-7
references.pmid: 388422
references.citation: Neurochem Res. 2011 Sep;36(9):1706-14
references.pmid: 21399908
references.citation: Lipids. 1977 Jun;12(6):455-68
references.pmid: 881947
references.citation: J Lipid Res. 2004 May;45(5):783-93
references.pmid: 15087476
references.citation: ASN Neuro. 2010 Oct 04;2(4):e00044
references.pmid: 20930939
references.citation: Nat Rev Neurosci. 2001 Nov;2(11):840-3
references.pmid: 11715061
references.citation: J Lipid Res. 1972 Sep;13(5):680-6
references.pmid: 5075512
references.citation: Nature. 1983 Jun 2-8;303(5916):390-6
references.pmid: 6304520
references.citation: J Neurochem. 1963 Sep;10:613-23
references.pmid: 14066623
references.citation: Biochim Biophys Acta. 1957 Jun;24(3):604-11
references.pmid: 13436486
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10662-7
references.pmid: 8855236
references.citation: Dement Geriatr Cogn Disord. 2002;14(3):128-36
references.pmid: 12218255
references.citation: Brain Res. 1993 Sep 24;623(1):83-8
references.pmid: 8221098
references.citation: Int J Alzheimers Dis. 2011 Jan 09;2011:193618
references.pmid: 21274438
references.citation: Ann N Y Acad Sci. 1998 Jun 19;845:232-9
references.pmid: 9668357
references.citation: J Biochem. 1992 Mar;111(3):287-90
references.pmid: 1587788
references.citation: J Neurochem. 1989 Sep;53(3):953-61
references.pmid: 2668446
references.citation: J Neurochem. 2007 Dec;103(6):2327-41
references.pmid: 17883393
references.citation: Brain Res Dev Brain Res. 1990 Mar 1;52(1-2):131-40
references.pmid: 2331781
references.citation: Neuroreport. 1992 Apr;3(4):341-4
references.pmid: 1515593
references.citation: J Biol Chem. 1992 Jun 25;267(18):12973-8
references.pmid: 1618794
references.citation: J Biol Chem. 2000 Sep 8;275(36):27901-8
references.pmid: 10846187
references.citation: Acta Neuropathol. 1991;81(6):626-31
references.pmid: 1909079
references.citation: Neurochem Res. 2004 Apr;29(4):857-67
references.pmid: 15098951
references.citation: J Biol Chem. 2002 Jan 18;277(3):1633-6
references.pmid: 11682464