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1.  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 
ASN NEURO  2013;5(2):e00113.
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.
doi:10.1042/AN20130006
PMCID: PMC3667643  PMID: 23565921
Alzheimer’s disease; amyloid β protein; Chol-1α ganglioside; transgenic mouse; Aβ, amyloid β-protein; AD, Alzheimer’s disease; APP, amyloid precursor protein; HPTLC, high-performance TLC; PSEN, presenilin; Tg, transgenic; WT, wild-type; GD3S or STII, GD3-synthase; mAb, monoclonal antibody; NeuNAc, N-acetylneuraminic acid or sialic acid
2.  Ganglioside metabolism in a transgenic mouse model of Alzheimer's disease: expression of Chol-1α antigens in the brain 
ASN NEURO  2010;2(4):e00044.
The accumulation of Aβ (amyloid β-protein) is one of the major pathological hallmarks in AD (Alzheimer's disease). Gangliosides, sialic acid-containing glycosphingolipids enriched in the nervous system and frequently used as biomarkers associated with the biochemical pathology of neurological disorders, have been suggested to be involved in the initial aggregation of Aβ. In the present study, we have examined ganglioside metabolism in the brain of a double-Tg (transgenic) mouse model of AD that co-expresses mouse/human chimaeric APP (amyloid precursor protein) with the Swedish mutation and human presenilin-1 with a deletion of exon 9. Although accumulation of Aβ was confirmed in the double-Tg mouse brains and sera, no statistically significant change was detected in the concentration and composition of major ganglio-N-tetraosyl-series gangliosides in the double-Tg brain. Most interestingly, Chol-1α antigens (cholinergic neuron-specific gangliosides), such as GT1aα and GQ1bα, which are minor species in the brain, were found to be increased in the double-Tg mouse brain. We interpret that the occurrence of these gangliosides may represent evidence for generation of cholinergic neurons in the AD brain, as a result of compensatory neurogenesis activated by the presence of Aβ.
doi:10.1042/AN20100021
PMCID: PMC2948441  PMID: 20930939
Alzheimer's disease; amyloid β-peptide; Chol-1α antigen; cholinergic neuron; ganglioside; transgenic mouse; Aβ, amyloid β-peptide; AD, Alzheimer's disease; APP, amyloid precursor protein; HPTLC, high-performance TLC; PSEN, presenilin; PSEN1dE9, PSEN-1 with a deletion of exon 9; Tg, transgenic; WT, wild-type

Results 1-2 (2)