title: Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices.
abstract: Synaptic train stimulation (10 Hz x 25 s) in hippocampal slices results in a biphasic response of NAD(P)H fluorescence indicating a transient oxidation followed by a prolonged reduction. The response is accompanied by a transient tissue PO(2) decrease indicating enhanced oxygen utilization. The activation of mitochondrial metabolism and/or glycolysis may contribute to the secondary NAD(P)H peak. We investigated whether extracellular lactate uptake via monocarboxylate transporters (MCTs) contributes to the generation of the NAD(P)H response during neuronal activation. We measured the effect of lactate uptake inhibition [using the MCT inhibitor alpha-cyano-4-hydroxycinnamate (4-CIN)] on the NAD(P)H biphasic response, tissue PO(2) response, and field excitatory post-synaptic potential in hippocampal slices during synaptic stimulation in area CA1 (stratum radiatum). The application of 4-CIN (150-250 micromol/L) significantly decreased the reduction phase of the NAD(P)H response. When slices were supplemented with 20 mmol/L lactate in 150-250 micromol/L 4-CIN, the secondary NAD(P)H peak was restored; whereas 20 mmol/L pyruvate supplementation did not produce a recovery. Similarly, the tissue PO(2) response was decreased by MCT inhibition; 20 mmol/L lactate restored this response to control levels at all 4-CIN concentrations. These results indicate that lactate uptake via MCTs contributes significantly to energy metabolism in brain tissue and to the generation of the delayed NAD(P)H peak after synaptic stimulation.
authors.affiliation: Neurosurgery, Neurobiology, Duke University Medical Center Research and Surgery Services, Durham VAMC, North Carolina 27710, USA. Galeffi@duke.edu
authors.forename: Francesca
authors.initials: F
authors.lastname: Galeffi
authors.forename: Kelley A
authors.initials: KA
authors.lastname: Foster
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Sadgrove
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Beaver
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Turner
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D009249:NADP / Q000378:metabolism*; D009924:Organ Culture Techniques; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D027501:Monocarboxylic Acid Transporters; D019344:Lactic Acid; D009249:NADP