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Ketogenic diet's effects on levels of energetic brain metabolites in rat.

Ketogenic diets (KD) have been used for close to a century to facilitate medically intractable epilepsy. The anticonvulsant effects of KD develop slowly with chronic ingestion but the molecular mechanisms that underlie its actions remain unidentified. We have previously reported that KD significantly increased the phosphocreatine to creatine ratio (PCr/Cr) in hippocampus of seizure-naive rat (1). After further analyses, we hypothesize that KD increases levels of high-energy metabolites in discrete rat brain regions. We measured by HPLC levels of adenine nucleotides, adenosine, phosphocreatine and creatine. Using a head-focused high-energy microwave system to quickly kill rats and instantly snap-inactivate brain enzymes, we observed significantly elevated levels of high-energy brain metabolites in rats fed KD. We observed increased PCr/Cr ratios, levels of ATP, and adenylate energy charge values in these discrete brain regions. KD-induced increases in levels of adenosine did not reach statistical significance in any of the tested regions. Electrophysiological recordings from KD-fed rats demonstrated changes in synaptic transmission as well as the influence of purines on synaptic transmission that were consistent with the alterations in adenylate energy charge and purine metabolism observed neurochemically. These anticonvulsant and neuroprotectant effects of KD may be owed to increased PCr/Cr ratios and a superior ability to maintain elevated levels of ATP. (Supported by NCRR P20RR017699 & MH065431 (JDG) & NS 29173 (SAM) & CT Space Grant (SAM & CCS))

(1) Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ.: Annuals of Neurology. 2006 Aug; 60 (2): 223-35.

Jeremy W. Gawryluk * (1), John F. Wagener (1), Jason Gockel (4), Daniel Coleman (3), Charles C. Swart (2,3), Susan A. Masino (2), Jonathan D. Geiger (1)

(1) Dept. of Pharmacology, Physiology, & Therapeutics, University of North Dakota, Grand Forks, ND

(2) Biology Dept., Trinity College, Hartford, CT

(3) Neuroscience Dept., Trinity College, Hartford, CT

(4) Psychology Dept., Trinity College, Hartford, CT
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Author:Gawryluk, Jeremy W.; Wagener, John F.; Gockel, Jason; Coleman, Daniel; Swart, Charles C. Masino, Sus
Publication:Proceedings of the North Dakota Academy of Science
Article Type:Report
Geographic Code:1USA
Date:Apr 1, 2008
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