Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-l-Carnitine

Hadera, Mussie Ghezu, McDonald, Tanya, Smeland, Olav B., Meisingset, Tore W., Eloqayli, Haytham, Jaradat, Saied, Borges, Karin and Sonnewald, Ursula (2015) Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-l-Carnitine. Neurochemical Research, 41 1-2: 86-95. doi:10.1007/s11064-015-1728-5


Author Hadera, Mussie Ghezu
McDonald, Tanya
Smeland, Olav B.
Meisingset, Tore W.
Eloqayli, Haytham
Jaradat, Saied
Borges, Karin
Sonnewald, Ursula
Title Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-l-Carnitine
Journal name Neurochemical Research   Check publisher's open access policy
ISSN 1573-6903
0364-3190
Publication date 2015-10-03
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s11064-015-1728-5
Open Access Status Not yet assessed
Volume 41
Issue 1-2
Start page 86
End page 95
Total pages 10
Place of publication New York, United States
Publisher Springer
Language eng
Abstract Epilepsy is a severe neurological disorder characterized by altered electrical activity in the brain. Important pathophysiological mechanisms include disturbed metabolism and homeostasis of major excitatory and inhibitory neurotransmitters, glutamate and GABA. Current drug treatments are largely aimed at decreasing neuronal excitability and thereby preventing the occurrence of seizures. However, many patients are refractory to treatment and side effects are frequent. Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults. In rodents, the pilocarpine-status epilepticus model reflects the pathology and chronic spontaneous seizures of TLE and the pentylenetetrazole kindling model exhibits chronic induced limbic seizures. Accumulating evidence from studies on TLE points to alterations in astrocytes and neurons as key metabolic changes. The present review describes interventions which alleviate these disturbances in astrocyte–neuronal interactions by supporting mitochondrial metabolism. The compounds discussed are the endogenous transport molecule acetyl-l-carnitine and the triglyceride of heptanoate, triheptanoin. Both provide acetyl moieties for oxidation in the tricarboxylic acid cycle whereas heptanoate is also provides propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis—the refilling of the tricarboxylic acid cycle.
Keyword Acetyl-l-carnitine
Triheptanoin
Epilepsy
Neurons
Astrocytes
Metabolism
Glucose
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 2 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 03 Nov 2015, 10:35:03 EST by System User on behalf of Scholarly Communication and Digitisation Service