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Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices.

Publication ,  Journal Article
Galeffi, F; Foster, KA; Sadgrove, MP; Beaver, CJ; Turner, DA
Published in: J Neurochem
December 2007

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.

Duke Scholars

Published In

J Neurochem

DOI

EISSN

1471-4159

Publication Date

December 2007

Volume

103

Issue

6

Start / End Page

2449 / 2461

Location

England

Related Subject Headings

  • Synaptic Transmission
  • Rats, Inbred F344
  • Rats
  • Presynaptic Terminals
  • Oxygen Consumption
  • Oxidative Phosphorylation
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • NADP
  • Monocarboxylic Acid Transporters
 

Citation

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Galeffi, F., Foster, K. A., Sadgrove, M. P., Beaver, C. J., & Turner, D. A. (2007). Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices. J Neurochem, 103(6), 2449–2461. https://doi.org/10.1111/j.1471-4159.2007.04939.x
Galeffi, Francesca, Kelley A. Foster, Matthew P. Sadgrove, Christopher J. Beaver, and Dennis A. Turner. “Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices.J Neurochem 103, no. 6 (December 2007): 2449–61. https://doi.org/10.1111/j.1471-4159.2007.04939.x.
Galeffi, Francesca, et al. “Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices.J Neurochem, vol. 103, no. 6, Dec. 2007, pp. 2449–61. Pubmed, doi:10.1111/j.1471-4159.2007.04939.x.
Journal cover image

Published In

J Neurochem

DOI

EISSN

1471-4159

Publication Date

December 2007

Volume

103

Issue

6

Start / End Page

2449 / 2461

Location

England

Related Subject Headings

  • Synaptic Transmission
  • Rats, Inbred F344
  • Rats
  • Presynaptic Terminals
  • Oxygen Consumption
  • Oxidative Phosphorylation
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • NADP
  • Monocarboxylic Acid Transporters