GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION

Citation
M. Ankarcrona et al., GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION, Neuron, 15(4), 1995, pp. 961-973
Citations number
63
Categorie Soggetti
Neurosciences
Journal title
NeuronACNP
ISSN journal
08966273
Volume
15
Issue
4
Year of publication
1995
Pages
961 - 973
Database
ISI
SICI code
0896-6273(1995)15:4<961:GND-AS>2.0.ZU;2-M
Abstract
During ischemic brain injury, glutamate accumulation leads to overstim ulation of postsynaptic glutamate receptors with intracellular Ca2+ ov erload 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 subpo pulation of neurons died by necrosis. In these cells, mitochondrial me mbrane potential collapsed, nuclei swelled, and intracellular debris w ere scattered in the incubation medium. Neurons surviving the early ne crotic phase recovered mitochondrial potential and energy levels. Late r, they underwent apoptosis, as shown by the formation of apoptotic nu clei and by chromatin degradation into high and low molecular weight f ragments. These results suggest that mitochondrial function is a criti cal factor that determines the mode of neuronal death in excitotoxicit y.