title: Monocarboxylate transporter 1 is deficient on microvessels in the human epileptogenic hippocampus.
abstract: Monocarboxylate transporter 1 (MCT1) facilitates the transport of important metabolic fuels (lactate, pyruvate and ketone bodies) and possibly also acidic drugs such as valproic acid across the blood-brain barrier. Because an impaired brain energy metabolism and resistance to antiepileptic drugs are common features of temporal lobe epilepsy (TLE), we sought to study the expression of MCT1 in the brain of patients with this disease. Immunohistochemistry and immunogold electron microscopy were used to assess the distribution of MCT1 in brain specimens from patients with TLE and concomitant hippocampal sclerosis (referred to as mesial TLE or MTLE (n=15)), patients with TLE and no hippocampal sclerosis (non-MTLE, n=13) and neurologically normal autopsy subjects (n=8). MCT1 was present on an extensive network of microvessels throughout the hippocampal formation in autopsy controls and to a lesser degree in non-MTLE. Patients with MTLE were markedly deficient in MCT1 on microvessels in several areas of the hippocampal formation, especially CA1, which exhibited a 37% to 48% loss of MCT1 on the plasma membrane of endothelial cells when compared with non-MTLE. These findings suggest that the uptake of blood-derived monocarboxylate fuels and possibly also acidic drugs, such as valproic acid, is perturbed in the epileptogenic hippocampus, particularly in MTLE. We hypothesize that the loss of MCT1 on brain microvessels is mechanistically involved in the pathophysiology of drug-resistant TLE, and propose that re-expression of MCT1 may represent a novel therapeutic approach for this disease.
authors.affiliation: The Brain and Muscle Energy Group, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105 Blindern, NO-0317 Oslo, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lauritzen
authors.forename: Nihal C
authors.initials: NC
authors.lastname: de Lanerolle
authors.forename: Tih-Shih W
authors.initials: TS
authors.lastname: Lee
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Spencer
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002536:Cerebral Arteries / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006624:Hippocampus / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000235:genetics*; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D027981:Symporters / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1