Cargando…

Molecular signature of extracellular matrix pathology in schizophrenia

Growing evidence points to a critical involvement of the extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Decreases of perineuronal nets (PNNs) and altered expression of chondroitin sulphate proteoglycans (CSPGs) in glial cells have been identified in several brain regions. G...

Descripción completa

Detalles Bibliográficos
Autores principales: Pantazopoulos, Harry, Katsel, Pavel, Haroutunian, Vahram, Chelini, Gabriele, Klengel, Torsten, Berretta, Sabina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359380/
https://www.ncbi.nlm.nih.gov/pubmed/33070392
http://dx.doi.org/10.1111/ejn.15009
_version_ 1783737537012957184
author Pantazopoulos, Harry
Katsel, Pavel
Haroutunian, Vahram
Chelini, Gabriele
Klengel, Torsten
Berretta, Sabina
author_facet Pantazopoulos, Harry
Katsel, Pavel
Haroutunian, Vahram
Chelini, Gabriele
Klengel, Torsten
Berretta, Sabina
author_sort Pantazopoulos, Harry
collection PubMed
description Growing evidence points to a critical involvement of the extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Decreases of perineuronal nets (PNNs) and altered expression of chondroitin sulphate proteoglycans (CSPGs) in glial cells have been identified in several brain regions. GWAS data have identified several SZ vulnerability variants of genes encoding for ECM molecules. Given the potential relevance of ECM functions to the pathophysiology of this disorder, it is necessary to understand the extent of ECM changes across brain regions, their region‐ and sex‐specificity and which ECM components contribute to these changes. We tested the hypothesis that the expression of genes encoding for ECM molecules may be broadly disrupted in SZ across several cortical and subcortical brain regions and include key ECM components as well as factors such as ECM posttranslational modifications and regulator factors. Gene expression profiling of 14 neocortical brain regions, caudate, putamen and hippocampus from control subjects (n = 14/region) and subjects with SZ (n = 16/region) was conducted using Affymetrix microarray analysis. Analysis across brain regions revealed widespread dysregulation of ECM gene expression in cortical and subcortical brain regions in SZ, impacting several ECM functional key components. SRGN, CD44, ADAMTS1, ADAM10, BCAN, NCAN and SEMA4G showed some of the most robust changes. Region‐, sex‐ and age‐specific gene expression patterns and correlation with cognitive scores were also detected. Taken together, these findings contribute to emerging evidence for large‐scale ECM dysregulation in SZ and point to molecular pathways involved in PNN decreases, glial cell dysfunction and cognitive impairment in SZ.
format Online
Article
Text
id pubmed-8359380
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-83593802021-08-17 Molecular signature of extracellular matrix pathology in schizophrenia Pantazopoulos, Harry Katsel, Pavel Haroutunian, Vahram Chelini, Gabriele Klengel, Torsten Berretta, Sabina Eur J Neurosci Special Issue Articles Growing evidence points to a critical involvement of the extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Decreases of perineuronal nets (PNNs) and altered expression of chondroitin sulphate proteoglycans (CSPGs) in glial cells have been identified in several brain regions. GWAS data have identified several SZ vulnerability variants of genes encoding for ECM molecules. Given the potential relevance of ECM functions to the pathophysiology of this disorder, it is necessary to understand the extent of ECM changes across brain regions, their region‐ and sex‐specificity and which ECM components contribute to these changes. We tested the hypothesis that the expression of genes encoding for ECM molecules may be broadly disrupted in SZ across several cortical and subcortical brain regions and include key ECM components as well as factors such as ECM posttranslational modifications and regulator factors. Gene expression profiling of 14 neocortical brain regions, caudate, putamen and hippocampus from control subjects (n = 14/region) and subjects with SZ (n = 16/region) was conducted using Affymetrix microarray analysis. Analysis across brain regions revealed widespread dysregulation of ECM gene expression in cortical and subcortical brain regions in SZ, impacting several ECM functional key components. SRGN, CD44, ADAMTS1, ADAM10, BCAN, NCAN and SEMA4G showed some of the most robust changes. Region‐, sex‐ and age‐specific gene expression patterns and correlation with cognitive scores were also detected. Taken together, these findings contribute to emerging evidence for large‐scale ECM dysregulation in SZ and point to molecular pathways involved in PNN decreases, glial cell dysfunction and cognitive impairment in SZ. John Wiley and Sons Inc. 2020-11-13 2021-06 /pmc/articles/PMC8359380/ /pubmed/33070392 http://dx.doi.org/10.1111/ejn.15009 Text en © 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Special Issue Articles
Pantazopoulos, Harry
Katsel, Pavel
Haroutunian, Vahram
Chelini, Gabriele
Klengel, Torsten
Berretta, Sabina
Molecular signature of extracellular matrix pathology in schizophrenia
title Molecular signature of extracellular matrix pathology in schizophrenia
title_full Molecular signature of extracellular matrix pathology in schizophrenia
title_fullStr Molecular signature of extracellular matrix pathology in schizophrenia
title_full_unstemmed Molecular signature of extracellular matrix pathology in schizophrenia
title_short Molecular signature of extracellular matrix pathology in schizophrenia
title_sort molecular signature of extracellular matrix pathology in schizophrenia
topic Special Issue Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359380/
https://www.ncbi.nlm.nih.gov/pubmed/33070392
http://dx.doi.org/10.1111/ejn.15009
work_keys_str_mv AT pantazopoulosharry molecularsignatureofextracellularmatrixpathologyinschizophrenia
AT katselpavel molecularsignatureofextracellularmatrixpathologyinschizophrenia
AT haroutunianvahram molecularsignatureofextracellularmatrixpathologyinschizophrenia
AT chelinigabriele molecularsignatureofextracellularmatrixpathologyinschizophrenia
AT klengeltorsten molecularsignatureofextracellularmatrixpathologyinschizophrenia
AT berrettasabina molecularsignatureofextracellularmatrixpathologyinschizophrenia