title: Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function.
abstract: During ischemic brain injury, glutamate accumulation leads to overstimulation of postsynaptic glutamate receptors with intracellular Ca2+ overload and neuronal cell death. Here we show that glutamate can induce either early necrosis or delayed apoptosis in cultures of cerebellar granule cells. During and shortly after exposure to glutamate, a subpopulation of neurons died by necrosis. In these cells, mitochondrial membrane potential collapsed, nuclei swelled, and intracellular debris were scattered in the incubation medium. Neurons surviving the early necrotic phase recovered mitochondrial potential and energy levels. Later, they underwent apoptosis, as shown by the formation of apoptotic nuclei and by chromatin degradation into high and low molecular weight fragments. These results suggest that mitochondrial function is a critical factor that determines the mode of neuronal death in excitotoxicity.
authors.affiliation: Division of Toxicology, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ankarcrona
authors.forename: J M
authors.initials: JM
authors.lastname: Dypbukt
authors.forename: E
authors.initials: E
authors.lastname: Bonfoco
authors.forename: B
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
authors.forename: S A
authors.initials: SA
authors.lastname: Lipton
authors.forename: P
authors.initials: P
authors.lastname: Nicotera
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002531:Cerebellum / Q000473:pathology*; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D008970:Molecular Weight; D009336:Necrosis / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002843:Chromatin; D018698:Glutamic Acid; D004247:DNA