The cerebral microvasculature in schizophrenia: a laser capture microdissection study.

<h4>Background</h4>Previous studies of brain and peripheral tissues in schizophrenia patients have indicated impaired energy supply to the brain. A number of studies have also demonstrated dysfunction of the microvasculature in schizophrenia patients. Together these findings are consiste...

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Autores principales: Laura W Harris, Matthew Wayland, Martin Lan, Margaret Ryan, Thomas Giger, Helen Lockstone, Irene Wuethrich, Michael Mimmack, Lan Wang, Mark Kotter, Rachel Craddock, Sabine Bahn
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Publicado: Public Library of Science (PLoS) 2008
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spelling oai:doaj.org-article:70b2569b333d4519a25dae37fa8816612021-11-25T06:18:09ZThe cerebral microvasculature in schizophrenia: a laser capture microdissection study.1932-620310.1371/journal.pone.0003964https://doaj.org/article/70b2569b333d4519a25dae37fa8816612008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19088852/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Previous studies of brain and peripheral tissues in schizophrenia patients have indicated impaired energy supply to the brain. A number of studies have also demonstrated dysfunction of the microvasculature in schizophrenia patients. Together these findings are consistent with a hypothesis of blood-brain barrier dysfunction in schizophrenia. In this study, we have investigated the cerebral vascular endothelium of schizophrenia patients at the level of transcriptomics.<h4>Methodology/principal findings</h4>We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from schizophrenia patients and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using two independent microarray platforms, Affymetrix HG133plus2.0 GeneChips and CodeLink Whole Human Genome arrays. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology. We then compared neuronal and endothelial data separately between schizophrenic subjects and controls. Analysis of the endothelial samples showed differences in gene expression between schizophrenics and controls which were reproducible in a second microarray platform. Functional profiling revealed that these changes were primarily found in genes relating to inflammatory processes.<h4>Conclusions/significance</h4>This study provides preliminary evidence of molecular alterations of the cerebral microvasculature in schizophrenia patients, suggestive of a hypo-inflammatory state in this tissue type. Further investigation of the blood-brain barrier in schizophrenia is warranted.Laura W HarrisMatthew WaylandMartin LanMargaret RyanThomas GigerHelen LockstoneIrene WuethrichMichael MimmackLan WangMark KotterRachel CraddockSabine BahnPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 12, p e3964 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Laura W Harris
Matthew Wayland
Martin Lan
Margaret Ryan
Thomas Giger
Helen Lockstone
Irene Wuethrich
Michael Mimmack
Lan Wang
Mark Kotter
Rachel Craddock
Sabine Bahn
The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
description <h4>Background</h4>Previous studies of brain and peripheral tissues in schizophrenia patients have indicated impaired energy supply to the brain. A number of studies have also demonstrated dysfunction of the microvasculature in schizophrenia patients. Together these findings are consistent with a hypothesis of blood-brain barrier dysfunction in schizophrenia. In this study, we have investigated the cerebral vascular endothelium of schizophrenia patients at the level of transcriptomics.<h4>Methodology/principal findings</h4>We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from schizophrenia patients and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using two independent microarray platforms, Affymetrix HG133plus2.0 GeneChips and CodeLink Whole Human Genome arrays. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology. We then compared neuronal and endothelial data separately between schizophrenic subjects and controls. Analysis of the endothelial samples showed differences in gene expression between schizophrenics and controls which were reproducible in a second microarray platform. Functional profiling revealed that these changes were primarily found in genes relating to inflammatory processes.<h4>Conclusions/significance</h4>This study provides preliminary evidence of molecular alterations of the cerebral microvasculature in schizophrenia patients, suggestive of a hypo-inflammatory state in this tissue type. Further investigation of the blood-brain barrier in schizophrenia is warranted.
format article
author Laura W Harris
Matthew Wayland
Martin Lan
Margaret Ryan
Thomas Giger
Helen Lockstone
Irene Wuethrich
Michael Mimmack
Lan Wang
Mark Kotter
Rachel Craddock
Sabine Bahn
author_facet Laura W Harris
Matthew Wayland
Martin Lan
Margaret Ryan
Thomas Giger
Helen Lockstone
Irene Wuethrich
Michael Mimmack
Lan Wang
Mark Kotter
Rachel Craddock
Sabine Bahn
author_sort Laura W Harris
title The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
title_short The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
title_full The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
title_fullStr The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
title_full_unstemmed The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
title_sort cerebral microvasculature in schizophrenia: a laser capture microdissection study.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/70b2569b333d4519a25dae37fa881661
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