title: Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients.
abstract: Postmortem and positron emission tomography studies have indicated the pathophysiological involvement of microglial cells in schizophrenia. We hypothesized that the microglial production of quinolinic acid (QUIN), an endogenous N-methyl-d-aspartate receptor (NMDAR) agonist, may be linked to the previously described glutamatergic deficits in the hippocampus of schizophrenia patients. We performed a semi-quantitative assessment of QUIN-immunoreactive microglial cells in schizophrenia patients and matched controls in the CA1, CA2/3, and dentate gyrus (DG) area of the posterior hippocampal formation. Complementary immunostaining of the commonly used microglial surface marker HLA-DR was performed in adjacent histological sections. Fewer QUIN-immunoreactive microglial cells were observed in the CA1 hippocampal subregion of schizophrenia patients compared to controls (left p=0.028, right p=0.018). No significant diagnosis-dependent changes were observed in the CA2/3 and DG regions. These results were controlled for potential confounds by age, duration of disease, autolysis time, psychotropic medication, and hippocampal volume. No diagnosis-related differences were observed for the overall density of microglial cells (HLA-DR expression). Our findings suggest that reduced microglial QUIN content in the hippocampal CA1 region is associated with schizophrenia. We hypothesize that this association may contribute to impaired glutamatergic neurotransmission in the hippocampus of schizophrenia patients.
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany; Institute of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gos
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany; Department of Psychiatry, University of Munich, Germany; School for Mental Health and Neuroscience, University of Maastricht, The Netherlands.
authors.forename: Aye-Mu
authors.initials: AM
authors.lastname: Myint
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Kolja
authors.initials: K
authors.lastname: Schiltz
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Meyer-Lotz
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Busse
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany.
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Müller
authors.affiliation: Institute of Neuropathology, University of Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany.
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany. Electronic address: johann.steiner@med.ovgu.de.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
mesh_terms: D000328:Adult; D056547:CA1 Region, Hippocampal / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D018690:Excitatory Amino Acid Agonists / Q000032:analysis*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology; D006684:HLA-DR Antigens / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D017628:Microglia / Q000737:chemistry* / Q000276:immunology; D008875:Middle Aged; D015213:Neuroimmunomodulation / Q000502:physiology; D009928:Organ Specificity; D017378:Quinolinic Acid / Q000032:analysis*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012559:Schizophrenia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission
chemical_list: D018690:Excitatory Amino Acid Agonists; D006684:HLA-DR Antigens; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D017378:Quinolinic Acid
keywords: Glutamate; Hippocampal formation; Hippocampus; Microglia; Quinolinic acid; Schizophrenia