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Decreased quinolinic acid in the hippocampus of depressive patients: evidence for local anti-inflammatory and neuroprotective responses?

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Abstract

Disturbances of glutamatergic neurotransmission and mononuclear phagocyte system activation have been described uni- and bipolar depression (UD/BD). Linking the glutamate and immune hypotheses of depression, quinolinic acid (QUIN) is synthesized by activated microglia and acts as an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist with neurotoxic properties. Recently, we observed an increased microglial QUIN expression in the subgenual and supracallosal, but not in the pregenual part of the anterior cingulate cortex in postmortem brains of suicide cases with severe depression. Since several hints point to a role of the hippocampus in depression, we extended our study and addressed the question whether microglial QUIN is also changed in subregions of the hippocampus (CA1 and CA2/3 areas) in these patients. Postmortem brains of 12 acutely depressed patients (UD, n = 6; BD, n = 6) and 10 neuropsychiatric healthy age- and gender-matched control subjects were analyzed using QUIN-immunohistochemistry. Hippocampal volumes were determined in order to assess possible neurotoxic or neurodegenerative aspects. Microglial QUIN expression in the whole group of depressed patients was either comparable (left CA1, right CA2/3) or decreased (right CA1: p = 0.004, left CA2/3: p = 0.044) relative to controls. Post hoc tests showed that QUIN was reduced both in UD and BD in the right CA1 field (UD, p = 0.048; BD, p = 0.031). No loss of hippocampal volume was detected. Our data indicate that UD and BD are associated with a local reduction in QUIN-immunoreactive microglia in the hippocampus and underline the importance of the NMDA-R signaling in depressive disorders.

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Acknowledgments

Gabriela Meyer-Lotz and Kathrin Paelchen provided excellent technical assistance. Prof. Christian Mawrin (Department of Neuropathology, University of Magdeburg, Germany) performed the routine neuropathological examinations of all tested brains.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatric Pulmonology, Allergology and Neonatology, Medical University of Hannover (MHH), Hannover, Germany

    Mandy Busse

  2. Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany

    Stefan Busse, Tomasz Gos, Henrik Dobrowolny, Ulf J. Müller, Bernhard Bogerts, Hans-Gert Bernstein & Johann Steiner

  3. Department of Psychiatry, Ludwig Maximilians University, Munich, Germany

    Aye Mu Myint

  4. School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands

    Aye Mu Myint

  5. Institute of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland

    Tomasz Gos

  6. Center for Behavioral Brain Sciences, Magdeburg, Germany

    Bernhard Bogerts & Johann Steiner

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Correspondence to Johann Steiner.

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Mandy Busse and Stefan Busse have contributed equally to this work.

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Busse, M., Busse, S., Myint, A.M. et al. Decreased quinolinic acid in the hippocampus of depressive patients: evidence for local anti-inflammatory and neuroprotective responses?. Eur Arch Psychiatry Clin Neurosci 265, 321–329 (2015). https://doi.org/10.1007/s00406-014-0562-0

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