Neuroprotective effects of extracellular glutamate are absent in hippocampal organotypic cultures treated with the amyloid peptide Abeta(25-35).
Hippocampal cells are particularly vulnerable in Alzheimer's disease but the cause of cell death is unknown. Amyloid toxicity has been implicated in hippocampal cell death, but its specific mechanisms are poorly understood. We used confocal microscopy to examine the effects of the amyloid peptide fragment 25-35 (Abeta(25-35)) on cell death in organotypic hippocampal slice cultures. Addition of glutamate to the culture medium significantly improved nerve cell survival in cultures subjected to consecutive medium exchanges. This effect was lost if cultures were treated with the amyloid peptide fragment Abeta(25-35) but not the inactive peptide 35-25. These data suggest that one of the mechanisms responsible for amyloid toxicity may be inhibition of the survival promoting effects of extracellular glutamate.
Baskys
A
A
Department of Physiology, University of Toronto, Toronto, Ontario, M5T 2S8, Canada. andrius.baskys@med.va.gov
Adamchik
Y
Y
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000633:toxicity*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space; D005419:Flavonoids / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000032:analysis; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018613:Microscopy, Confocal; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology / Q000633:toxicity*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011419:Propidium / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects; D000077191:Wortmannin
D016229:Amyloid beta-Peptides; D000730:Androstadienes; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017470:Receptors, Glutamate; C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25); D011419:Propidium; D018698:Glutamic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin