Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures

Primary dissociated neuronal cultures have been intensively exploited for the past 15 years as model systems to investigate excitotoxic neuronal degeneration. Even this simplified system contains a complex web of interactions between calcium homeostasis, ATP production and the generation and detoxification of reactive oxygen species. There is increasing realization that the mitochondrion occupies the center stage in these processes. This review covers the normal bioenergetics of the cultured neuron, the ways in which mitochondrial dysfunction impacts upon the ability of the neuron to withstand excitotoxic stress, the nature of the stresses imposed by NMDA receptor activation and possible molecular mechanisms of excitotoxic cell death.