| NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function. | |
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MedLine Citation:
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PMID: 16538234 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Excitatory stimulation in hippocampal slices results in biphasic NAD(P)H fluorescence transients. Previous studies using differing stimulus protocols agreed that the oxidation phase is a consequence of mitochondrial metabolism, but the reduction phase has been attributed to (1) mitochondrial nicotinamide adenine dinucleotide (NADH) generation or (2) astrocytic glycolysis triggered by glutamate uptake. In an attempt to reconcile these two views, the present study examined NAD(P)H signals evoked by a wide range of stimulus durations (40 ms to 20 secs). A combination of ionotropic glutamate receptor (iGluR) antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-5-phosphonopentanoic acid (APV)) virtually abolished responses to brief stimuli (40 to 200 ms, 50 Hz), but a significant fraction of the signal elicited by extended stimulation (20 secs, 32 Hz) was resistant to CNQX/APV. Glycolysis was inhibited by removal of glucose and addition of 2-deoxyglucose (2DG) (10 mmol/L) or iodoacetic acid (IAA, 1 mmol/L). Pyruvate was provided as an alternative substrate for oxidative phosphorylation and the A1 receptor antagonist 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) included to prevent decreases in synaptic efficacy. If sufficient pyruvate was supplied, responses to brief and extended stimuli were unaffected by glycolytic inhibition and not significantly reduced by an inhibitor of glucose uptake (3-O-methyl glucose, 3 mmol/L). When timed to arrive at the peak of overshoots generated by extended synaptic stimulation, brief pyruvate applications (10 mmol/L, 2 mins) had little effect on evoked NAD(P)H increases. Flavoprotein autofluorescence transients after extended stimuli matched (with inverted sign) NAD(P)H responses. Responses to extended stimuli were not reduced by a nonselective inhibitor of glutamate uptake DL-Threo-beta-benzyloxyaspartic acid (TBOA). These results suggest that NAD(P)H transients report mitochondrial dynamics, rather than recruitment of glycolytic metabolism, over a wide range of stimulus intensities. |
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Authors:
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Angela M Brennan; John A Connor; C William Shuttleworth |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-03-15 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 26 ISSN: 0271-678X ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-10-24 Completed Date: 2006-11-14 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1389-406 Citation Subset: IM |
Affiliation:
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Department of Neurosciences, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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2-Amino-5-phosphonovalerate
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pharmacology 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology Animals Bicuculline / pharmacology Brain / physiology* Electric Stimulation Excitatory Amino Acid Antagonists / pharmacology Excitatory Postsynaptic Potentials / physiology Flavoproteins / metabolism Fluorescence GABA Antagonists / pharmacology Glutamic Acid / metabolism Glycolysis / drug effects, physiology Long-Term Potentiation / drug effects Male Mice Mice, Inbred C57BL Mitochondria / physiology* NADP / metabolism* Neuroglia / physiology Neurons / physiology Pyruvates / metabolism Synapses / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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NS43458/NS/NINDS NIH HHS; RR15636/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Excitatory Amino Acid Antagonists; 0/Flavoproteins; 0/GABA Antagonists; 0/Pyruvates; 115066-14-3/6-Cyano-7-nitroquinoxaline-2,3-dione; 485-49-4/Bicuculline; 53-59-8/NADP; 56-86-0/Glutamic Acid; 76726-92-6/2-Amino-5-phosphonovalerate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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