Redistribution of monocarboxylate transporter 2 on the surface of astrocytes in the human epileptogenic hippocampus

Authors

  • Fredrik Lauritzen,

    1. The Brain and Muscle Energy Group, Department of Anatomy and Centre for Molecular Biology and Neuroscience, University of Oslo, Blindern, NO-0317 Oslo, Norway
    2. Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
    3. Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
    4. Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Kjell Heuser,

    1. Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Nihal C. de Lanerolle,

    1. Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
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  • Tih-Shih W. Lee,

    1. Department of Psychiatry Yale University School of Medicine, New Haven, Connecticut
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  • Dennis D. Spencer,

    1. Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
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  • Jung H. Kim,

    1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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  • Albert Gjedde,

    1. Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
    2. Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    3. Department of Clinical Medicine, Aarhus University Hospital, Brendstrupgårdsvej 100, DK-8200 Aarhus N, Denmark
    4. Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada
    5. Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Tore Eid,

    Corresponding author
    1. Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
    • The Brain and Muscle Energy Group, Centre for Molecular Biology and Neuroscience, Department of Anatomy and Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105 Blindern, NO-0317 Oslo, Norway or Tore Eid, Department of Laboratory Medicine, Yale University School of Medicine, 330 Cedar Street, P.O. Box 208035, New Haven, CT 06520-8035, USA
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  • Linda H. Bergersen

    Corresponding author
    1. The Brain and Muscle Energy Group, Department of Anatomy and Centre for Molecular Biology and Neuroscience, University of Oslo, Blindern, NO-0317 Oslo, Norway
    2. Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
    3. Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    • The Brain and Muscle Energy Group, Centre for Molecular Biology and Neuroscience, Department of Anatomy and Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105 Blindern, NO-0317 Oslo, Norway or Tore Eid, Department of Laboratory Medicine, Yale University School of Medicine, 330 Cedar Street, P.O. Box 208035, New Haven, CT 06520-8035, USA
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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. © 2012 Wiley Periodicals, Inc.

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