title: Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats.
abstract: Glucose is the primary carbon source to enter the adult brain for catabolic and anabolic reactions. Some studies suggest that astrocytes may metabolize glucose to lactate; the latter serving as a preferential substrate for neurons, especially during neuronal activation. The current study utilizes the aconitase inhibitor fluorocitrate to differentially inhibit oxidative metabolism in glial cells in vivo. Oxidative metabolism of 14C-lactate and 14C-glucose was monitored in vivo using microdialysis and quantitating 14CO2 in the microdialysis eluate following pulse labeling of the interstitial glucose or lactate pool. After establishing a baseline oxidation rate, fluorocitrate was added to the perfusate. Neither lactate nor glucose oxidation was affected by 5 micromol/L fluorocitrate. However, 20 and 100 micromol/L fluorocitrate reduced lactate oxidation by 55 +/- 20% and 68 +/- 12%, respectively (p < 0.05 for both). Twenty and 100 micromol/L fluorocitrate reduced 14C-glucose oxidation by 50 +/- 14% (p < 0.05) and 24 +/- 19% (ns), respectively. Addition of non-radioactive lactate to (14)C-glucose plus fluorocitrate decreased 14C-glucose oxidation by an additional 29% and 38%, respectively. These results indicate that astrocytes oxidize about 50% of the interstitial lactate and about 35% of the glucose. By subtraction, neurons metabolize a maximum of 50% of the interstitial lactate and 65% of the interstitial glucose.
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21010, USA. rzielke@umaryland.edu
authors.forename: H Ronald
authors.initials: HR
authors.lastname: Zielke
authors.forename: Carol L
authors.initials: CL
authors.lastname: Zielke
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Baab
authors.forename: J Tyson
authors.initials: JT
authors.lastname: Tildon
mesh_terms: D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009068:Movement / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002250:Carbon Radioisotopes; D002951:Citrates; D004791:Enzyme Inhibitors; D007773:Lactates; C007744:fluorocitrate; D000154:Aconitate Hydratase; D005947:Glucose