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Physiological Oxygen Level Is Critical for Modeling Neuronal Metabolism In Vitro
- Physiological Oxygen Level Is Critical for Modeling Neuronal Metabolism In Vitro
- 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
- Journal of Neuroscience Research, 90(2), 422-434
- Article Type
- Adenosine Triphosphate; Adenylate Kinase; AMPK; Animal Cell; Animals; Brain Cell; Brain Cortex; Brain Mitochondrion; Brain Oxygen Consumption; Cell Metabolism; Cell Stress; Cell Survival; Cell Viability; Cells, Cultured; Cerebral Cortex; Controlled Study; Culture; Energy Metabolism; Enzyme Activation; Enzyme Activity; Enzyme Inhibition; Fatty Acid Oxidation; Female; Glucose; Glucose Oxidation; Glucose Transport; Glycolysis; Metabolism; Models, Neurological; Nerve Cell Culture; Neuron; Neurons; Non-Human; Oxidation-Reduction State; Oxygen; Oxygen Consumption; Pregnancy; Priority Journal; Rat; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species (ROS); Tissue Oxygenation
- 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.
- Wiley Blackwell
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- Brain and Cognitive SciencesETC1. Journal Articles
Brain and Cognitive SciencesETC1. Journal Articles
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