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Physiological Oxygen Level Is Critical for Modeling Neuronal Metabolism In Vitro

Title
Physiological Oxygen Level Is Critical for Modeling Neuronal Metabolism In Vitro
Authors
Zhu, J[Zhu, Jing]Aja, S[Aja, Susan]Kim, EK[Kim, Eun-Kyoung]Park, MJ[Park, Min Jung]Ramamurthy, S[Ramamurthy, Santosh]Jia, JL[Jia, Junling]Hu, XY[Hu, Xueying]Geng, P[Geng, Ping]Ronnett, GV[Ronnett, Gabriele V.]
DGIST Authors
Kim, EK[Kim, Eun-Kyoung]; Ronnett, GV[Ronnett, Gabriele V.]
Issue Date
2012-02
Citation
Journal of Neuroscience Research, 90(2), 422-434
Type
Article
Article Type
Article
Keywords
Adenosine TriphosphateAdenylate KinaseAMPKAnimal CellAnimalsBrain CellBrain CortexBrain MitochondrionBrain Oxygen ConsumptionCell MetabolismCell StressCell SurvivalCell ViabilityCells, CulturedCerebral CortexControlled StudyCultureEnergy MetabolismEnzyme ActivationEnzyme ActivityEnzyme InhibitionFatty Acid OxidationFemaleGlucoseGlucose OxidationGlucose TransportGlycolysisMetabolismModels, NeurologicalNerve Cell CultureNeuronNeuronsNon-HumanOxidation-Reduction StateOxygenOxygen ConsumptionPregnancyPriority JournalRatRatsRats, Sprague-DawleyReactive Oxygen Species (ROS)Tissue Oxygenation
ISSN
0360-4012
Abstract
In vitro models are important tools for studying the mechanisms that govern neuronal responses to injury. Most neuronal culture methods employ nonphysiological conditions with regard to metabolic parameters. Standard neuronal cell culture is performed at ambient (21%) oxygen levels, whereas actual tissue oxygen levels in the mammalian brain range from 1% to 5%. In this study, we examined the consequences of oxygen level on the viability and metabolism of primary cultures of cortical neurons. Our results indicate that physiological oxygen level (5% O 2) has a beneficial effect on cortical neuronal survival and mitochondrial function in vitro. Moreover, oxygen level affects metabolic fluxes: glucose uptake and glycolysis was enhanced at physiological oxygen level, whereas glucose oxidation and fatty acid oxidation were reduced. Adenosine monophosphate-activated protein kinase (AMPK) was more activated in 5% O 2 and appears to play a role in these metabolic effects. Inhibiting AMPK activity with compound C decreased glucose uptake, intracellular ATP level, and viability in neurons cultured in 5% O 2. These data indicate that oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro. © 2011 Wiley Periodicals, Inc.
URI
http://hdl.handle.net/20.500.11750/3388
DOI
10.1002/jnr.22765
Publisher
Wiley Blackwell
Related Researcher
Files:
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Collection:
Brain and Cognitive SciencesETC1. Journal Articles
Brain and Cognitive SciencesETC1. Journal Articles


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