Cytotoxic effects of G(M1) ganglioside and amyloid beta-peptide on mouse embryonic neural stem cells.

Hdl Handle:
http://hdl.handle.net/10675.2/64
Title:
Cytotoxic effects of G(M1) ganglioside and amyloid beta-peptide on mouse embryonic neural stem cells.
Authors:
Yanagisawa, Makoto; Ariga, Toshio; Yu, Robert K.
Abstract:
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 Abetas (amyloid beta-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Abetas. Several reports have documented the bifunctional roles of Abetas in NSCs (neural stem cells), but the precise effects of G(M1) and Abeta on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Abeta-(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 G(M1) or Abeta-(1-40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Abeta-(1-40). The exogenously added G(M1) and Abeta-(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 G(M1) and Abeta-(1-40), but caspase 3 was activated. NECs treated with G(M1) and Abeta-(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 G(M1) and Abeta-(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 Abeta-(1-40) and G(M1) 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.
Citation:
ASN Neuro. 2010 Mar 15; 2(1):e00029
Issue Date:
22-Mar-2010
URI:
http://hdl.handle.net/10675.2/64
DOI:
10.1042/AN20090063
PubMed ID:
20305711
PubMed Central ID:
PMC2838405
Type:
Journal Article
ISSN:
1759-0914
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorYanagisawa, Makotoen_US
dc.contributor.authorAriga, Toshioen_US
dc.contributor.authorYu, Robert K.en_US
dc.date.accessioned2010-09-24T21:26:50Z-
dc.date.available2010-09-24T21:26:50Z-
dc.date.issued2010-03-22en_US
dc.identifier.citationASN Neuro. 2010 Mar 15; 2(1):e00029en_US
dc.identifier.issn1759-0914en_US
dc.identifier.pmid20305711en_US
dc.identifier.doi10.1042/AN20090063en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/64-
dc.description.abstractAD (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 Abetas (amyloid beta-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Abetas. Several reports have documented the bifunctional roles of Abetas in NSCs (neural stem cells), but the precise effects of G(M1) and Abeta on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Abeta-(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 G(M1) or Abeta-(1-40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Abeta-(1-40). The exogenously added G(M1) and Abeta-(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 G(M1) and Abeta-(1-40), but caspase 3 was activated. NECs treated with G(M1) and Abeta-(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 G(M1) and Abeta-(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 Abeta-(1-40) and G(M1) 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.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.titleCytotoxic effects of G(M1) ganglioside and amyloid beta-peptide on mouse embryonic neural stem cells.en_US
dc.typeJournal Articleen_US
dc.identifier.pmcidPMC2838405en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Geneticsen_US
dc.contributor.corporatenameInstitute of Neuroscienceen_US

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.