Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis

Authors

  • Ludmyla Kandratavicius,

    1. Department of Neurosciences and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
    2. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
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  • Pedro Rosa-Neto,

    1. Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Douglas Research Institute, McGill University, Montreal, Canada
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  • Mariana Raquel Monteiro,

    1. Department of Neurosciences and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
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  • Marie-Christine Guiot,

    1. Department of Pathology, Montreal Neurological Institute, McGill University, Montreal, Canada
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  • Joao Alberto Assirati Jr,

    1. Department of Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
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  • Carlos Gilberto Carlotti Jr,

    1. Department of Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
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  • Eliane Kobayashi,

    1. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
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  • Joao Pereira Leite

    Corresponding author
    1. Department of Neurosciences and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
    • Correspondence to: Joao Pereira Leite, Ribeirao Preto Medical School, Department of Neurosciences and Behavior, University of Sao Paulo, Av Bandeirantes 3900, 14049-900, Ribeirao Preto, SP, Brazil. E-mail: jpleite@fmrp.usp.br

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  • The copyright line for this article was changed on 26 February 2015 after original online publication.

ABSTRACT

Metabotropic glutamate receptor type 5 (mGluR5) upregulation in temporal lobe epilepsy (TLE) and the correlation of its expression with features of hippocampal sclerosis (HS) remains unclear. Here we characterized mGluR5 immunoreactivity in hippocampus, entorhinal cortex (EC), and subiculum of TLE specimens with confirmed HS, with neocortical TLE (non-HS) and necropsy controls. We correlated mGluR5 immunoreactivity with neuronal density, mossy fiber sprouting, astrogliosis (GFAP), and dendritic alterations (MAP2). TLE specimens showed increased mGluR5 expression, which was most pronounced in the EC, subiculum, CA2, and dentate gyrus outer molecular layer. Increased mGluR5 expression was seen in hippocampal head and body segments and was independent of neuronal density, astrogliosis, or dendritic alterations. Positive correlation between mGluR5 expression with mossy fiber sprouting and with MAP2 in CA3 and CA1 was found only in HS specimens. Negative correlation between mGluR5 expression with seizure frequency and epilepsy duration was found only in non-HS cases. Specimens from HS patients without previous history of febrile seizure (FS) showed higher mGluR5 and MAP2 expression in CA2. Our study suggests that mGluR5 upregulation is part of a repertoire of post-synaptic adaptations that might control overexcitation and excessive glutamate release rather than a dysfunction that leads to seizure facilitation. That would explain why non-HS cases, on which seizures are likely to originate outside the hippocampal formation, also exhibit upregulated mGluR5. On the other hand, lower mGluR5 expression was related to increased seizure frequency. In addition to its role in hyperexcitability, mGluR5 upregulation could play a role in counterbalance mechanisms along the hyperexcitable circuitry uniquely altered in sclerotic hippocampal formation. Inefficient post-synaptic compensatory morphological (dendritic branching) and glutamatergic (mGluR5 expression) mechanisms in CA2 subfield could potentially underlie the association of FS with HS and TLE. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

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