Cytotoxic effects of GM1 ganglioside and amyloid β-peptide on mouse embryonic neural stem cells

Makoto Yanagisawa, Toshio Ariga, Robert K. Yu

Research output: Contribution to journalArticle

13 Scopus citations

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 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 NECswere 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 G M1 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.

Original languageEnglish (US)
Article numbere00029
Pages (from-to)49-56
Number of pages8
JournalASN Neuro
Volume2
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Alzheimer's disease (AD)
  • Amyloid β-peptide (Aβ)
  • Apoptosis
  • Glycosphingolipid
  • Neural stem cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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