Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients

Brain, Behavior, and Immunity

Volumn 41, Issue 1, 2014, Pages 59-64

  Gos, Tomasz ^a,b   Myint, Aye Mu ^a,c,d   Schiltz, Kolja ^a,e   Meyer Lotz, Gabriela ^a   Dobrowolny, Henrik ^a   Busse, Stefan ^a   Müller, Ulf J ^a   Mawrin, Christian ^a   Bernstein, Hans Gert ^a   Bogerts, Bernhard ^a,e   Steiner, Johann ^a,e  

^a OTTO VON GUERICKE UNIVERSITY   (Germany)

^b MEDICAL UNIVERSITY OF GDANSK   (Poland)

^c UNIVERSITY OF MUNICH   (Germany)

^d MAASTRICHT UNIVERSITY   (Netherlands)

^e CENTER FOR BEHAVIORAL BRAIN SCIENCES   (Germany)

Author keywords

Glutamate; Hippocampal formation; Hippocampus; Microglia; Quinolinic acid; Schizophrenia

Indexed keywords

HLA DR ANTIGEN; N METHYL DEXTRO ASPARTIC ACID RECEPTOR STIMULATING AGENT; QUINOLINIC ACID; AMINO ACID RECEPTOR STIMULATING AGENT; GLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR;

ADULT; ANTIBODY LABELING; ARTICLE; CELL COUNT; CELL DENSITY; CLINICAL ARTICLE; CONTROLLED STUDY; DENTATE GYRUS; DISEASE DURATION; DSM-IV; FEMALE; HIPPOCAMPAL CA1 REGION; HIPPOCAMPAL CA2 REGION; HIPPOCAMPAL CA3 REGION; HUMAN; HUMAN TISSUE; IMMUNOCOMPETENT CELL; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MACROPHAGE; MALE; MICROGLIA; MIDDLE AGED; MONOCYTE; PARANOID SCHIZOPHRENIA; PRIORITY JOURNAL; PROTEIN EXPRESSION; SCHIZOPHRENIA; AGONISTS; ANTIBODY SPECIFICITY; CHEMISTRY; HIPPOCAMPUS; IMMUNOLOGY; IMMUNOMODULATION; METABOLISM; PATHOLOGY; PHYSIOLOGY; SYNAPTIC TRANSMISSION;

ADULT; CA1 REGION, HIPPOCAMPAL; CELL COUNT; EXCITATORY AMINO ACID AGONISTS; FEMALE; GLUTAMIC ACID; HIPPOCAMPUS; HLA-DR ANTIGENS; HUMANS; MALE; MICROGLIA; MIDDLE AGED; NEUROIMMUNOMODULATION; ORGAN SPECIFICITY; QUINOLINIC ACID; RECEPTORS, N-METHYL-D-ASPARTATE; SCHIZOPHRENIA; SYNAPTIC TRANSMISSION;

EID: 84924080573     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2014.05.012     Document Type: Article

References (39)

1. Bergink V., Gibney S.M., Drexhage H.A. Autoimmunity, inflammation and psychosis: a Search for peripheral markers. Biol. Psychiatr. 2013, 75:324-331.
2. Bernstein H.G., Klix M., Dobrowolny H., Brisch R., Steiner J., Bielau H., Gos T., Bogerts B. A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders. Eur. Arch. Psychiatry Clin. Neurosci. 2012, 262:637-646.
3. Bogerts B. The temporolimbic system theory of positive schizophrenic symptoms. Schizophr. Bull. 1997, 23:423-435.
4. Busse S., Busse M., Schiltz K., Bielau H., Gos T., Brisch R., Mawrin C., Schmitt A., Jordan W., Muller U.J., Bernstein H.G., Bogerts B., Steiner J. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?. Brain Behav. Immun. 2012, 26:1273-1279.
5. Doorduin J., de Vries E.F., Willemsen A.T., de Groot J.C., Dierckx R.A., Klein H.C. Neuroinflammation in schizophrenia-related psychosis: a PET study. J. Nucl. Med. 2009, 50:1801-1807.
6. Dowlati Y., Herrmann N., Swardfager W., Liu H., Sham L., Reim E.K., Lanctot K.L. A meta-analysis of cytokines in major depression. Biol. Psychiatry 2010, 67:446-457.
7. Drexhage R.C., Knijff E.M., Padmos R.C., Heul-Nieuwenhuijzen L., Beumer W., Versnel M.A., Drexhage H.A. The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Rev. Neurother. 2010, 10:59-76.
8. Erhardt S., Blennow K., Nordin C., Skogh E., Lindstrom L.H., Engberg G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci. Lett. 2001, 313:96-98.
9. Frank M.G., Baratta M.V., Sprunger D.B., Watkins L.R., Maier S.F. Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav. Immun. 2007, 21:47-59.
10. Guillemin G.J., Smythe G., Takikawa O., Brew B.J. Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons. Glia 2005, 49:15-23.
11. Heyes M.P. Quinolinic acid and inflammation. Ann. N. Y. Acad. Sci. 1993, 679:211-216.
12. Hsu S.M., Soban E. Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J. Histochem. Cytochem. 1982, 30:1079-1082.
13. Lisman J.E., Coyle J.T., Green R.W., Javitt D.C., Benes F.M., Heckers S., Grace A.A. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci. 2008, 31:234-242.
14. Mai J.K., Assheuer J., Paxinos G. Atlas of the Human Brain 2003, Academic Press, San Diego.
15. Miller B.J., Buckley P., Seabolt W., Mellor A., Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol. Psychiatry 2011, 70:663-671.
16. Miller C.L., Llenos I.C., Dulay J.R., Barillo M.M., Yolken R.H., Weis S. Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol. Dis. 2004, 15:618-629.
17. Miller C.L., Llenos I.C., Dulay J.R., Weis S. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res. 2006, 1073-1074:25-37.
18. Myint A.M. Kynurenines: from the perspective of major psychiatric disorders. FEBS J. 2012, 279:1375-1385.
19. Polak M., Haymaker W., Johnson J.E., ĎAmelio F Neuroglia and their reactions. Histology and Histopathology of the Nervous System 1982, 363-480. Charles C. Thomas Publishing, Springfield. W. Haymaker, R.D. Adams (Eds.).
20. Potvin S., Stip E., Sepehry A.A., Gendron A., Bah R., Kouassi E. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol. Psychiatry 2008, 63:801-808.
21. Santamaria A., Jimenez-Capdeville M.E., Camacho A., Rodriguez-Martinez E., Flores A., Galvan-Arzate S. In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum. NeuroReport 2001, 12:2693-2696.
22. Sathyasaikumar K.V., Stachowski E.K., Wonodi I., Roberts R.C., Rassoulpour A., McMahon R.P., Schwarcz R. Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr. Bull. 2011, 37:1147-1156.
23. Schmitt A., Steyskal C., Bernstein H.G., Schneider-Axmann T., Parlapani E., Schaeffer E.L., Gattaz W.F., Bogerts B., Schmitz C., Falkai P. Stereologic investigation of the posterior part of the hippocampus in schizophrenia. Acta Neuropathol. 2009, 117:395-407.
24. Schwarcz R., Bruno J.P., Muchowski P.J., Wu H.Q. Kynurenines in the mammalian brain: when physiology meets pathology. Nat. Rev. Neurosci. 2012, 13:465-477.
25. Schwarcz R., Rassoulpour A., Wu H.Q., Medoff D., Tamminga C.A., Roberts R.C. Increased cortical kynurenate content in schizophrenia. Biol. Psychiatry 2001, 50:521-530.
26. Small S.A., Schobel S.A., Buxton R.B., Witter M.P., Barnes C.A. A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat. Rev. Neurosci. 2011, 12:585-601.
27. Snyder M.A., Gao W.J. NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Front. Cell. Neurosci. 2013, 7:31.
28. Steiner J., Bielau H., Brisch R., Danos P., Ullrich O., Mawrin C., Bernstein H.G., Bogerts B. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J. Psychiatr. Res. 2008, 42:151-157.
29. Steiner J., Bogerts B., Sarnyai Z., Walter M., Gos T., Bernstein H.G., Myint A.M. Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: Potential role of glial NMDA receptor modulators and impaired blood-brain barrier integrity. World J. Biol. Psychiatry 2012, 13:482-492.
30. Steiner J., Gos T., Bogerts B., Bielau H., Drexhage H.A., Bernstein H.G. Possible impact of microglial cells and the monocyte-macrophage system on suicidal behavior. CNS Neurol. Disord.: Drug Targets 2013, 12:971-979.
31. Steiner J., Mawrin C., Ziegeler A., Bielau H., Ullrich O., Bernstein H.G., Bogerts B. Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathol. 2006, 112:305-316.
32. Steiner J., Walter M., Gos T., Guillemin G.J., Bernstein H.G., Sarnyai Z., Mawrin C., Brisch R., Bielau H., Meyerzu Schwabedissen L, Bogerts B, Myint A.M Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission?. J. Neuroinflamm. 2011, 8:94.
33. Stone T.W., Perkins M.N. Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. Eur. J. Pharmacol. 1981, 72:411-412.
34. Stone T.W., Stoy N., Darlington L.G. An expanding range of targets for kynurenine metabolites of tryptophan. Trends Pharmacol. Sci. 2013, 34:136-143.
35. van Berckel B.N., Bossong M.G., Boellaard R., Kloet R., Schuitemaker A., Caspers E., Luurtsema G., Windhorst A.D., Cahn W., Lammertsma A.A., Kahn R.S. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol. Psychiatry 2008, 64:820-822.
36. Wonodi I., Stine O.C., Sathyasaikumar K.V., Roberts R.C., Mitchell B.D., Hong L.E., Kajii Y., Thaker G.K., Schwarcz R. Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch. Gen. Psychiatry 2011, 68:665-674.
37. Wu J.Q., Kosten T.R., Zhang X.Y. Free radicals, antioxidant defense systems, and schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013, 46:200-206.
38. Yang C.R., Svensson K.A. Allosteric modulation of NMDA receptor via elevation of brain glycine and D-serine: the therapeutic potentials for schizophrenia. Pharmacol. Ther. 2008, 120:317-332.
39. Zierhut K.C., Grassmann R., Kaufmann J., Steiner J., Bogerts B., Schiltz K. Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia. Brain 2013, 136:804-814.