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1.  Expression of GD2 and GD3 gangliosides in human embryonic neural stem cells 
ASN NEURO  2011;3(2):e00054.
NSCs (neural stem cells) are undifferentiated neural cells endowed with a high potential for proliferation and a capacity for self-renewal with retention of multipotency to differentiate into neurons and glial cells. It has been recently reported that GD3, a b-series ganglioside, is a marker molecule for identifying and isolating mouse NSCs. However, the expression of gangliosides in human NSCs is largely unknown. In the present study, we analysed the expression of gangliosides, GD2 and GD3, in human NSCs that were isolated from human brains at gestational week 17 in the form of neurospheres, which are floating clonal aggregates formed by NSCs in vitro. Employing immunocytochemistry, we found that human NSCs were strongly reactive to anti-GD2 antibody and relatively weakly reactive to anti-GD3 antibody. Treatment of these cells with an organic solvent such as 100% methanol, which selectively removes glycolipids from plasma membrane, abolished the immunoreactivity with those antibodies, indicating that the reactivity was due to GD2 and GD3, but not to GD2-/GD3-like glycoproteins or proteoglycans. The immunoreactivity of human NSCs to antibody against SSEA-1 (stage-specific embryonic antigen-1), a well-known carbohydrate antigen of NSCs, was not decreased by the treatment with 100% methanol, indicating that SSEA-1 is mainly carried by glycoproteins and/or proteoglycans in human NSCs. Our study suggests that GD2 and GD3 can be marker gangliosides for identifying human NSCs.
doi:10.1042/AN20110006
PMCID: PMC3072763  PMID: 21395555
ganglioside; glycosphingolipid (GSL); neural stem cell (NSC); neurosphere; stage-specific embryonic antigen-1 (SSEA-1); bFGF, basic fibroblast growth factor; GSL, glycosphingolipid; LAMP-1, lysosome-associated membrane protein-1; NSC, neural stem cell; SSEA-1, stage-specific embryonic antigen-1. Abbreviations for gangliosides follow Svennerholm's nomenclature system (Svennerholm, 1963)
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
3.  Cytotoxic effects of GM1 ganglioside and amyloid β-peptide on mouse embryonic neural stem cells 
ASN NEURO  2010;2(1):e00029.
AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between GM1 ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of GM1 and Aβ on NSCs have not yet been clarified. We evaluated the effect of GM1 and Aβ-(1–40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either GM1 or Aβ-(1–40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of GM1 and Aβ-(1–40). The exogenously added GM1 and Aβ-(1–40) were confirmed to incorporate into NECs. The Ras–MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with GM1 and Aβ-(1–40), but caspase 3 was activated. NECs treated with GM1 and Aβ-(1–40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that GM1 and Aβ-(1–40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Aβ-(1–40) and GM1 co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling.
doi:10.1042/AN20090063
PMCID: PMC2838405  PMID: 20305711
Alzheimer’s disease (AD); amyloid β-peptide (Aβ); apoptosis; GM1 ganglioside; glycosphingolipid; neural stem cell; Aβ, amyloid β-peptide; AD, Alzheimer’s disease; bFGF, basic fibroblast growth factor; biotin-Ctxb, biotin-conjugated cholera toxin B subunit; CCD, charge-coupled device; DMEM, Dulbecco’s modified Eagle’s medium; ERK, extracellular-signal-regulated kinase; FITC-Aβ-(1–40), FITC-conjugated Aβ-(1–40); GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IACUC, Institutional Animal Care and Use Committee; IL, interleukin; MAP2, microtubule-associated protein 2; MAPK, mitogen-activated protein kinase; N2-DMEM/F12, N2-supplemented DMEM/Ham’s Nutrient Mixture F12; NEC, neuroepithelial cell; NSC, neural stem cell; RT–PCR, reverse transcription–PCR; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling

Results 1-3 (3)