TY - JOUR
T1 - Brain gangliosides of a transgenic mouse model of Alzheimer's disease with deficiency in GD3-synthase
T2 - Expression of elevated levels of a cholinergic-specific ganglioside, GT1aα
AU - Ariga, Toshio
AU - Itokazu, Yutaka
AU - McDonald, Michael P.
AU - Hirabayashi, Yoshio
AU - Ando, Susumu
AU - Yu, Robert K.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid β protein
KW - Chol-1 α ganglioside
KW - Transgenic mouse
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U2 - 10.1042/AN20130006
DO - 10.1042/AN20130006
M3 - Article
C2 - 23565921
AN - SCOPUS:84880980912
SN - 1759-0914
VL - 5
SP - 141
EP - 148
JO - ASN Neuro
JF - ASN Neuro
IS - 2
ER -