Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

Willis, Sarah, Stoll, James, Sweetman, Lawrence and Borges, Karin (2010) Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models. Neurobiology of Disease, 40 3: 565-572.

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Author Willis, Sarah
Stoll, James
Sweetman, Lawrence
Borges, Karin
Title Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models
Journal name Neurobiology of Disease  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2010-12
Sub-type Article
DOI 10.1016/j.nbd.2010.07.017
Volume number 40
Issue number 3
ISSN 0969-9961; 1095-953X
Start page 565
End page 572
Total pages 8
Place of publication Maryland Heights, United States
Publisher Academic Press
Collection year 2011
Language eng
Subject 11 Medical and Health Sciences
Formatted abstract We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0–35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined.
© 2010 Elsevier Inc. All rights reserved.
Keyword β-Hydroxybutyrate
Anaplerosis
Corneal kindling
Epilepsy
Pentylenetetrazole
Pilocarpine
Propionyl-CoA
Seizure
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Mon, 15 Nov 2010, 17:53:16 EST by Dr Karin Borges on behalf of School of Biomedical Sciences