Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats

• Published in: Journal of neurochemistry 2007-04, Vol.101 (1), p.9-16
• Main Authors: Zielke, H. Ronald, Zielke, Carol L, Baab, Peter J, Tildon, J. Tyson
• Format: Article
• Language: English
• Subjects: aconitase; aconitate hydratase; Aconitate Hydratase - antagonists & inhibitors; Aconitate Hydratase - metabolism; Animals; Astrocytes - metabolism; Biological and medical sciences; brain; Carbon Radioisotopes; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Citrates - pharmacology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; energy metabolism; Energy Metabolism - drug effects; Energy Metabolism - physiology; Enzyme Inhibitors - pharmacology; fluorocitrate; Glucose; Glucose - metabolism; Inhibitor drugs; Lactates - metabolism; Male; Medical sciences; Metabolism; Microdialysis; Movement - physiology; Neurology; Neurons; Neurons - metabolism; Neurosciences; Oxidation; Oxidative Phosphorylation - drug effects; Rats; Rats, Sprague-Dawley; Rodents; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04335.x

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 and¹⁴C-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 μmol/L fluorocitrate. However, 20 and 100 μmol/L fluorocitrate reduced lactate oxidation by 55 ± 20% and 68 ± 12%, respectively (p < 0.05 for both). Twenty and 100 μmol/L fluorocitrate reduced ¹⁴C-glucose oxidation by 50 ± 14% (p < 0.05) and 24 ± 19% (ns), respectively. Addition of non-radioactive lactate to ¹⁴C-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.