The glutamate hypothesis of depression: a possible role for glutamate transporters in the pathophysiology of MDD

Thomas Demuyser, Teresa Femenía, Niels Danbolt, Joeri Van Liefferinge, Eduard-Mihai Bentea, Ellen Merckx, M. Lindskog, Ann Massie, Ilse Julia Smolders

Research output: Unpublished contribution to conferenceUnpublished abstract

Abstract

Glutamate uptake transporter expression is affected in the pleasure center of a rat model of depression
Thomas Demuyser1, Teresa Femenía 2, Niels Danbolt3, Joeri Van Liefferinge1, Eduard Bentea1, Ellen Merckx1, Maria Lindskog2, Ann Massie1, Ilse Smolders1
1Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium
2Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
3Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Depression is usually related to changes in the monoaminergic system. Half a century after the formulation of this hypothesis, compelling evidence points at an important role of glutamate in the etiology of the depressed brain. We have used the flinders sensitive line (FSL) rat model of depression to reveal possible mechanisms that underlie the depressed state. In previous research we unveiled changes in glutamate homeostasis in the hippocampus of the FSL rats: a decrease in D-serine and of GLAST expression (Gomez-Galan et al., Molecular Psychiatry, 10.1038 2012). Here we investigated the expression level of the astrocytic high affinity excitatory amino acid transporters (EAATs) in the nucleus accumbens, since this brain area is closely related to one of the major symptoms of depression, anhedonia. We observed a significant downregulation of GLT-1 and GLAST by Western blot in the FSL rats in comparison to the Sprague Dawley controls. Since glutamate uptake through the EAATs is of utmost importance to protect the neurons from excitotoxicity, disturbances in these uptake mechanisms can lead to important changes in the excitatory neurotransmission. These findings contribute to the characterization of the FSL model and since the nucleus accumbens is the pleasure center, it would be interesting to look at anhedonic behavior of the FSL rats after the administration of a chronic stressor. We hypothesize that the lower expression of the EAATs can be sufficient for glutamate uptake in basal conditions, but could be insufficient to compensate for the higher levels of glutamate after chronic stress.
Original languageEnglish
Publication statusPublished - 2013
EventResearch in Psychiatry Day Belg. College for Neuropsychopharmacology and Biological Psychiatr (BCNBP) - Leuven, Belgium
Duration: 27 Sep 2013 → …

Conference

ConferenceResearch in Psychiatry Day Belg. College for Neuropsychopharmacology and Biological Psychiatr (BCNBP)
CountryBelgium
CityLeuven
Period27/09/13 → …

Keywords

  • Glutamate uptake
  • Flinders Sensitive Line rat
  • Depression

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