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Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia

Authors

  • Akihito Uezato,

    1. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
    2. Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
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  • James H Meador-Woodruff,

    1. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
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  • Robert E McCullumsmith

    1. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
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  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Corresponding author:
Robert E. McCullumsmith, M.D., Ph.D.
Department of Psychiatry and Behavioral Neurobiology
University of Alabama at Birmingham School of Medicine
Civitan International Research Center, Room 576A
1530 3rd Avenue South
Birmingham, AL 35294, USA
Fax: (205) 975-4879
E-mail: smithrob@uab.edu

Abstract

Background:  Altered glutamate transmission has been found in the medial temporal lobe in severe psychiatric illnesses, including major depressive disorder (MDD) and bipolar disorder (BD). The vesicular glutamate transporters (VGLUTs) have a pivotal role in presynaptic release of glutamate into the synaptic cleft. We investigated this presynaptic marker in major psychiatric illness by measuring transcript expression of the VGLUTs in the medial temporal lobe.

Methods:  The study sample comprised four groups of 13 subjects with MDD, BD, or schizophrenia (SCZ), and a comparison group from the Stanley Foundation Neuropathology Consortium. In situ hybridization was performed to quantify messenger RNA (mRNA) expression of VGLUT 1, 2, and 3 in medial temporal lobe structures. We also examined the same areas of rats treated with antidepressants, a mood stabilizer, and antipsychotics to assess the effects of these medications on VGLUT mRNA expression.

Results:  We found decreased VGLUT1 mRNA expression in both MDD and BD in the entorhinal cortex (ERC), decreased VGLUT2 mRNA expression in MDD in the middle temporal gyrus, and increased VGLUT2 mRNA expression in SCZ in the inferior temporal gyrus (ITG). We also found a negative correlation between age and VGLUT1 mRNA expression in BD in the ERC and ITG. We did not find any changes in VGLUT mRNA expression in the hippocampus in any diagnostic group. We found decreased VGLUT1 mRNA expression in rats treated with haloperidol in the temporal cortex.

Conclusions:  These data indicate region-specific alterations of presynaptic glutamate innervation in the medial temporal lobe in the mood disorders.

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