title: Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures.
abstract: 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.
authors.affiliation: Buck Institute for Age Research, Novato, California, USA. dnicholls@buckinstitute.org
authors.forename: D G
authors.initials: DG
authors.lastname: Nicholls
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D004579:Electron Transport; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D008954:Models, Biological; D009336:Necrosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism; D013569:Synapses
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D025261:Mitochondrial Proton-Translocating ATPases; D005978:Glutathione; D010100:Oxygen; D002118:Calcium