title: Redistribution of monocarboxylate transporter 2 on the surface of astrocytes in the human epileptogenic hippocampus.
abstract: Emerging evidence points to monocarboxylates as key players in the pathophysiology of temporal lobe epilepsy (TLE) with hippocampal sclerosis (mesial temporal lobe epilepsy, MTLE). Monocarboxylate transporters (MCTs) 1 and 2, which are abundantly present on brain endothelial cells and perivascular astrocyte endfeet, respectively, facilitate the transport of monocarboxylates and protons across cell membranes. Recently, we reported that the density of MCT1 protein is reduced on endothelial cells and increased on astrocyte plasma membranes in the hippocampal formation in patients with MTLE and in several animal models of the disorder. Because the perivascular astrocyte endfeet comprise an important part of the neurovascular unit, we now assessed the distribution of the MCT2 in hippocampal formations in TLE patients with (MTLE) or without hippocampal sclerosis (non-MTLE). Light microscopic immunohistochemistry revealed significantly less perivascular MCT2 immunoreactivity in the hippocampal formation in MTLE (n = 6) than in non-MTLE (n = 6) patients, and to a lesser degree in non-MTLE than in nonepilepsy patients (n = 4). Immunogold electron microscopy indicated that the loss of MCT2 protein occurred on perivascular astrocyte endfeet. Interestingly, the loss of MCT2 on astrocyte endfeet in MTLE (n = 3) was accompanied by an upregulation of the protein on astrocyte membranes facing synapses in the neuropil, when compared with non-MTLE (n = 3). We propose that the altered distribution of MCT1 and MCT2 in TLE (especially MTLE) limits the flux of monocarboxylates across the blood-brain barrier and enhances the exchange of monocarboxylates within the brain parenchyma.
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy and Centre for Molecular Biology and Neuroscience, University of Oslo, Blindern, NO-0317 Oslo, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lauritzen
authors.forename: Kjell
authors.initials: K
authors.lastname: Heuser
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: Albert
authors.initials: A
authors.lastname: Gjedde
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D019581:Neuropil / Q000378:metabolism
chemical_list: D027501:Monocarboxylic Acid Transporters; C490427:SLC16A7 protein, human