Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients.
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.
['Gos|Tomasz|T|', 'Myint|Aye-Mu|AM|', 'Schiltz|Kolja|K|', 'Meyer-Lotz|Gabriela|G|', 'Dobrowolny|Henrik|H|', 'Busse|Stefan|S|', 'Müller|Ulf J|UJ|', 'Mawrin|Christian|C|', 'Bernstein|Hans-Gert|HG|', 'Bogerts|Bernhard|B|', 'Steiner|Johann|J|']
D000328:Adult D056547:CA1 Region, Hippocampal D002452:Cell Count D018690:Excitatory Amino Acid Agonists D005260:Female D018698:Glutamic Acid D006684:HLA-DR Antigens D006624:Hippocampus D006801:Humans D008297:Male D017628:Microglia D008875:Middle Aged D015213:Neuroimmunomodulation D009928:Organ Specificity D017378:Quinolinic Acid D016194:Receptors, N-Methyl-D-Aspartate D012559:Schizophrenia D009435:Synaptic Transmission
Quinolinic acid Hippocampus Schizophrenia Hippocampal formation Glutamate Microglia