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Acute Hypoxia Increases Neuronal Lactate and Superoxide Production and Decreases Intracellular pH in Neurons of the Nucleus Tractus Solitarius (NTS)
The FASEB Journal
  • Trevor Downing
  • Robert W. Putnam, Wright State University - Main Campus
  • Dominic P. D'Agostino
  • Jay B. Dean
Document Type
Conference Proceeding
Publication Date
4-1-2007
Catalog Record
Catalog Record
Abstract
Acute hypoxia (AH) and pro-oxidants acidify NTS neurons. We have tested the hypothesis that acidification during AH in rat brain slices (P1–12) is due to increased neuronal uptake of lactate produced by glia and superoxide generated by neurons. Intracellular pH and superoxide were measured, respectively, using the fluorogenic probes BCECF and dihydroethidium. The magnitude of acidification (–0.13 to –0.18 pH units) during AH (95% to 0% O2 for 10 min, ~37°C) was studied during metabolic inhibition using fluorocitrate (FC), a glial toxin, to abolish lactate production; 4-hydroxycinnamate (4-Cinn) to block neuronal uptake of glial lactate; O2-glucose deprivation (OGD) to reduce neuronal lactate production, and; iodoacetate (IodoA) to inhibit neuronal lactate production. FC and 4-Cinn did not block acidification during AH in NTS neurons (and retrotrapezoid nucleus neurons, which have a greater proportion of glia). OGD decreased acidification during AH by 25% in 40% of NTS neurons tested and IodoA decreased acidification during AH by 53%. Superoxide production increased during AH. The antioxidants melatonin and MnTMPyP decreased superoxide production and acidosis by 30% during AH. We conclude that acidification of NTS neurons during AH is caused primarily by lactate production by neurons and not glia, and increased intracellular superoxide production. ONR N000140410172, NIH R01HL56683.
Comments

Presented at the 2007 Federation of American Societies for Experimental Biology (FASEB) Science Research Conference.

Presentation Number 762.7.

Citation Information
Trevor Downing, Robert W. Putnam, Dominic P. D'Agostino and Jay B. Dean. "Acute Hypoxia Increases Neuronal Lactate and Superoxide Production and Decreases Intracellular pH in Neurons of the Nucleus Tractus Solitarius (NTS)" The FASEB Journal Vol. 21 Iss. Meeting Abstract Supplement (2007) p. A922 ISSN: 0892-6638
Available at: http://works.bepress.com/robert_putnam/56/