title: Monocarboxylate transporters in temporal lobe epilepsy: roles of lactate and ketogenic diet.
abstract: Epilepsy is a serious neurological disorder that affects approximately 1 % of the general population, making it one of the most common disorders of the central nervous system. Furthermore, up to 40 % of all patients with epilepsy cannot control their seizures with current medications. More efficacious treatments for medication refractory epilepsy are therefore needed. A better understanding of the mechanisms that cause this disorder is likely to facilitate the discovery of such treatments. Impairment in cerebral energy metabolism has been proposed as a possible causative factor in the pathogenesis of temporal lobe epilepsy (TLE), which is one of the most common types of medication-refractory epilepsies in adults. In this review, we will discuss some of the current hypotheses regarding the possible causal relationship between brain energy metabolism and TLE. Emphasis will be placed on the role of energy substrates (lactate and ketone bodies) and their transporter molecules, particularly monocarboxylate transporters 1 and 2 (MCT1 and MCT2). We recently reported that the cellular distribution of MCT1 and MCT2 is perturbed in the hippocampus in patients with TLE. The changes may be an adaptive response aimed at keeping high levels of lactate in the epileptic tissue, which may serve to counteract epileptic activity by downregulating cAMP levels through the lactate receptor GPR81, newly discovered in hippocampus. We propose that the perturbation of MCTs may be further involved in the pathophysiology of TLE by influencing brain energy homeostasis, mitochondrial function, GABA-ergic and glutamatergic neurotransmission, and flux of lactate through the brain.
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy and Department of Oral Biology, University of Oslo, P.O. Box 1105, Blindern, 0317, Oslo, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lauritzen
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
mesh_terms: D000818:Animals; D055423:Diet, Ketogenic / Q000379:methods*; D004833:Epilepsy, Temporal Lobe / Q000178:diet therapy* / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*
chemical_list: D027501:Monocarboxylic Acid Transporters; D019344:Lactic Acid