title: Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-L-Carnitine.
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.
authors.affiliation: Department of Pharmacy, College of Health Sciences, Mekelle University, Tigray, Ethiopia.
authors.forename: Mussie Ghezu
authors.initials: MG
authors.lastname: Hadera
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: McDonald
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407, Oslo, Norway.
authors.forename: Olav B
authors.initials: OB
authors.lastname: Smeland
authors.affiliation: Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway.
authors.forename: Tore W
authors.initials: TW
authors.lastname: Meisingset
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Haytham
authors.initials: H
authors.lastname: Eloqayli
authors.affiliation: Princes Haya Biotechnology Center, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Saied
authors.initials: S
authors.lastname: Jaradat
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: Borges
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Olav Kyrresgt. 3, 7489, Trondheim, Norway. ursula.sonnewald@ntnu.no.
authors.forename: Ursula
authors.initials: U
authors.lastname: Sonnewald
mesh_terms: D000108:Acetylcarnitine / Q000627:therapeutic use*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001253:Astrocytes / Q000378:metabolism*; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D014280:Triglycerides / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D000927:Anticonvulsants; D018377:Neurotransmitter Agents; D014280:Triglycerides; C531010:triheptanoin; D000108:Acetylcarnitine
keywords: Acetyl-L-carnitine; Astrocytes; Epilepsy; Glucose; Metabolism; Neurons; Triheptanoin