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

Toshio Ariga, Yutaka Itokazu, Michael P. McDonald, Yoshio Hirabayashi, Susumu Ando, Robert K. Yu

Research output: Contribution to journalArticle

15 Citations (Scopus)

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-/- triplemutant 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.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalASN Neuro
Volume5
Issue number2
DOIs
StatePublished - Aug 7 2013

Fingerprint

Gangliosides
Cholinergic Agents
Transgenic Mice
Alzheimer Disease
Brain
Cholinergic Neurons
Presenilins
Amyloid beta-Protein Precursor
Genes
trisialoganglioside GT1
alpha-N-acetylneuraminate alpha-2,8-sialyltransferase

Keywords

  • Alzheimer's disease
  • Amyloid β protein
  • Chol-1 α ganglioside
  • Transgenic mouse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

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. / Ariga, Toshio; Itokazu, Yutaka; McDonald, Michael P.; Hirabayashi, Yoshio; Ando, Susumu; Yu, Robert K.

In: ASN Neuro, Vol. 5, No. 2, 07.08.2013, p. 141-148.

Research output: Contribution to journalArticle

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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-/- triplemutant 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.",
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