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

Mandy Busse, Stefan Busse, Aye Mu Myint, Tomasz Gos, Henrik Dobrowolny, Ulf J. Mueller, Bernhard Bogerts, Hans-Gert Bernstein, Johann Steiner*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)321-329
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume265
Issue number4
DOIs
Publication statusPublished - Jun 2015

Keywords

  • Major depression
  • Bipolar disorder
  • Quinolinic acid
  • Monocytes
  • Microglia
  • Kynurenines
  • Glutamate

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