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
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.