NDLI: Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

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Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

Content Provider	Springer Nature Link
Author	Laird, Melissa D. Clerc, Pascaline Polster, Brian M. Fiskum, Gary
Copyright Year	2013
Abstract	Mitochondrial respiratory capacity is critical for responding to changes in neuronal energy demand. One approach toward neuroprotection is the administration of alternative energy substrates (“biofuels”) to overcome brain injury-induced inhibition of glucose-based aerobic energy metabolism. This study tested the hypothesis that exogenous pyruvate, lactate, β-hydroxybutyrate, and acetyl-l-carnitine each increase neuronal respiratory capacity in vitro either in the absence of or following transient excitotoxic glutamate receptor stimulation. Compared to the presence of 5 mM glucose alone, the addition of pyruvate, lactate, or β-hydroxybutyrate (1.0–10.0 mM) to either day in vitro (DIV) 14 or 7 rat cortical neurons resulted in significant, dose-dependent stimulation of respiratory capacity, measured by cell respirometry as the maximal O$_{2}$ consumption rate in the presence of the respiratory uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. A 30-min exposure to 100 μM glutamate impaired respiratory capacity for DIV 14, but not DIV 7, neurons. Glutamate reduced the respiratory capacity for DIV 14 neurons with glucose alone by 25 % and also reduced respiratory capacity with glucose plus pyruvate, lactate, or β-hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons following pyruvate or β-hydroxybutyrate addition was still, at least, as high as that obtained with glucose alone in the absence of glutamate exposure. These results support the interpretation that previously observed neuroprotection by exogenous pyruvate, lactate, or β-hydroxybutyrate is at least partially mediated by their preservation of neuronal respiratory capacity.
Starting Page	643
Ending Page	651
Page Count	9
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	4
Issue Number	6
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2013-08-10
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Excitotoxicity Energy metabolism Pyruvate Lactate β-Hydroxybutyrate Acetyl-l-carnitine Mitochondria Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

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