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

Makoto Yanagisawa, Toshio Ariga, Robert K. Yu

Research output: Contribution to journalArticle

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 Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of G(M1) and Aβ on NSCs have not yet been clarified. We evaluated the effect of G(M1) 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 G(M1) or Aβ-(1-40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Aβ-(1-40). The exogenously added G(M1) 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 G(M1) and Aβ-(1-40), but caspase 3 was activated. NECs treated with G(M1) 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 G(M1) 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 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.

Original languageEnglish (US)
JournalASN Neuro
Volume2
Issue number1
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Neuroepithelial Cells
G(M1) Ganglioside
Neural Stem Cells
Amyloid
Peptides
Alzheimer Disease
Cell Death
Sphingomyelins
DNA Nucleotidylexotransferase
Amyloid Plaques
Cellular Structures
Mouse Embryonic Stem Cells
Mitogen-Activated Protein Kinases
Caspase 3
Neurodegenerative Diseases
Dementia
Cell Count
Cholesterol
Cell Proliferation
Cell Membrane

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells. / Yanagisawa, Makoto; Ariga, Toshio; Yu, Robert K.

In: ASN Neuro, Vol. 2, No. 1, 01.12.2010.

Research output: Contribution to journalArticle

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