title: Primary cortical neuronal cultures reduce cellular energy utilization during anoxic energy deprivation.
abstract: It has been widely hypothesized that neurons reduce cellular energy use in response to periods of energy deprivation. To test this hypothesis, we measured rates of energy use under normoxia and anoxia in immature (6 days in vitro) and mature (13 days in vitro) neuronal cultures. During anoxic incubation immature and mature cultures reduced cellular energy use by 80% and 45%, respectively. Reduced cellular energy use dramatically affected ATP depletion in neuronal cultures under anoxia. Intracellular ATP stores were expected to deplete within 3 min of anoxia. However, ATP was maintained at decreased but stabilized concentrations for at least 3 h. The capacity of neuronal cultures to reduce cellular energy use during anoxia correlated with their sensitivity towards simulated ischemia. Immature cultures, with the largest capacity to reduce cellular energy use, survived simulated ischemia 2.5 times longer than mature cultures. The addition of glutamate receptor antagonists to mature cultures further decreased cellular energy use during anoxia and significantly extended their survival time under simulated ischemia. This study verifies that primary cortical neuronal cultures reduce cellular energy use during energy deprivation. Additionally, we show that maturation of glutamate receptor activity increases non-depressible energy demand in neuronal cultures.
authors.affiliation: Department of Biochemistry, The University of Western Australia, Crawley, Australia.
authors.forename: Shane E
authors.initials: SE
authors.lastname: Munns
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
authors.forename: Peter G
authors.initials: PG
authors.lastname: Arthur
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004734:Energy Metabolism / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity; D006003:Glycogen / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D010100:Oxygen