The Cerebral Microvasculature in Schizophrenia: A Laser Capture Microdissection Study

• Published in: PloS one Vol. 3; no. 12; p. e3964
• Main Authors: Harris, Laura W., Wayland, Matthew, Lan, Martin, Ryan, Margaret, Giger, Thomas, Lockstone, Helen, Wuethrich, Irene, Mimmack, Michael, Wang, Lan, Kotter, Mark, Craddock, Rachel, Bahn, Sabine
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.12.2008; Public Library of Science (PLoS)
• Subjects: Adult; Algorithms; Autopsy; Biochemistry/Bioinformatics; Biotechnology; Blood-brain barrier; Brain - blood supply; Brain - metabolism; Brain - pathology; Brain research; Case-Control Studies; Cell Biology/Gene Expression; Cell Biology/Neuronal and Glial Cell Biology; Chemical engineering; Consent; DNA microarrays; Endothelial cells; Endothelium; Epigenetics; Female; Gene expression; Gene Expression Profiling; Genomes; Genomics; Glucose; Humans; Hypotheses; Inflammation; Laser Therapy - methods; Lasers; Male; Medical research; Mental disorders; Mental Health/Schizophrenia and Other Psychoses; Metabolism; Microdissection - methods; Microvasculature; Microvessels - surgery; Middle Aged; Neurological Disorders/Neuropsychiatric Disorders; Neurons; Neuropathology; Neuroscience; Oligonucleotide Array Sequence Analysis; Patients; Ribonucleic acid; RNA; Rodents; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Schizophrenia - surgery; Studies; Tissues; Young Adult; United Kingdom > UK
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003964

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. 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. 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.