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Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

BACKGROUND: Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of th...

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Autores principales: Steiner, Johann, Walter, Martin, Gos, Tomasz, Guillemin, Gilles J, Bernstein, Hans-Gert, Sarnyai, Zoltán, Mawrin, Christian, Brisch, Ralf, Bielau, Hendrik, zu Schwabedissen, Louise Meyer, Bogerts, Bernhard, Myint, Aye-Mu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177898/
https://www.ncbi.nlm.nih.gov/pubmed/21831269
http://dx.doi.org/10.1186/1742-2094-8-94
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author Steiner, Johann
Walter, Martin
Gos, Tomasz
Guillemin, Gilles J
Bernstein, Hans-Gert
Sarnyai, Zoltán
Mawrin, Christian
Brisch, Ralf
Bielau, Hendrik
zu Schwabedissen, Louise Meyer
Bogerts, Bernhard
Myint, Aye-Mu
author_facet Steiner, Johann
Walter, Martin
Gos, Tomasz
Guillemin, Gilles J
Bernstein, Hans-Gert
Sarnyai, Zoltán
Mawrin, Christian
Brisch, Ralf
Bielau, Hendrik
zu Schwabedissen, Louise Meyer
Bogerts, Bernhard
Myint, Aye-Mu
author_sort Steiner, Johann
collection PubMed
description BACKGROUND: Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described. METHODS: Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA) glutamate receptor agonist quinolinic acid (QUIN) in the subgenual anterior cingulate cortex (sACC), anterior midcingulate cortex (aMCC) and pregenual anterior cingulate cortex (pACC) of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5) was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects. RESULTS: Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003) and the aMCC (P = 0.015) compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558). Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD. CONCLUSIONS: These results add a novel link to the immune hypothesis of depression by providing evidence for an upregulation of microglial QUIN in brain regions known to be responsive to infusion of NMDA antagonists such as ketamine. Further work in this area could lead to a greater understanding of the pathophysiology of depressive disorders and pave the way for novel NMDA receptor therapies or immune-modulating strategies.
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spelling pubmed-31778982011-09-22 Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission? Steiner, Johann Walter, Martin Gos, Tomasz Guillemin, Gilles J Bernstein, Hans-Gert Sarnyai, Zoltán Mawrin, Christian Brisch, Ralf Bielau, Hendrik zu Schwabedissen, Louise Meyer Bogerts, Bernhard Myint, Aye-Mu J Neuroinflammation Research BACKGROUND: Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described. METHODS: Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA) glutamate receptor agonist quinolinic acid (QUIN) in the subgenual anterior cingulate cortex (sACC), anterior midcingulate cortex (aMCC) and pregenual anterior cingulate cortex (pACC) of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5) was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects. RESULTS: Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003) and the aMCC (P = 0.015) compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558). Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD. CONCLUSIONS: These results add a novel link to the immune hypothesis of depression by providing evidence for an upregulation of microglial QUIN in brain regions known to be responsive to infusion of NMDA antagonists such as ketamine. Further work in this area could lead to a greater understanding of the pathophysiology of depressive disorders and pave the way for novel NMDA receptor therapies or immune-modulating strategies. BioMed Central 2011-08-10 /pmc/articles/PMC3177898/ /pubmed/21831269 http://dx.doi.org/10.1186/1742-2094-8-94 Text en Copyright ©2011 Steiner et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Steiner, Johann
Walter, Martin
Gos, Tomasz
Guillemin, Gilles J
Bernstein, Hans-Gert
Sarnyai, Zoltán
Mawrin, Christian
Brisch, Ralf
Bielau, Hendrik
zu Schwabedissen, Louise Meyer
Bogerts, Bernhard
Myint, Aye-Mu
Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?
title Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?
title_full Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?
title_fullStr Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?
title_full_unstemmed Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?
title_short Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?
title_sort severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission?
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177898/
https://www.ncbi.nlm.nih.gov/pubmed/21831269
http://dx.doi.org/10.1186/1742-2094-8-94
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