Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study

Abstract Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypot...

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Main Authors: Johanna Wallensten, Anna Nager, Marie Åsberg, Kristian Borg, Aniella Beser, Alexander Wilczek, Fariborz Mobarrez
Format: Article
Language:English
Published: Nature Publishing Group 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-81453-8
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spelling doaj-41a62f0acb5e4040b204e2e07776b14c2021-01-24T12:29:49ZengNature Publishing GroupScientific Reports2045-23222021-01-011111910.1038/s41598-021-81453-8Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional studyJohanna Wallensten0Anna Nager1Marie Åsberg2Kristian Borg3Aniella Beser4Alexander Wilczek5Fariborz Mobarrez6Academic Primary Health Care Centre, Region StockholmDivision of Family Medicine and Primary Health Care, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDepartment of Clinical Sciences, Karolinska Institutet, Danderyd University HospitalDepartment of Clinical Sciences, Karolinska Institutet, Danderyd University HospitalDepartment of Clinical Sciences, Karolinska Institutet, Danderyd University HospitalDepartment of Clinical Sciences, Karolinska Institutet, Danderyd University HospitalDepartment of Medical Sciences, Uppsala UniversityAbstract Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-derived EVs could be higher in patients with SED than in patients with major depressive disorder (MDD) and healthy controls. Patients with SED (n = 31), MDD (n = 31), and healthy matched controls (n = 61) were included. Astrocyte-derived EVs (previously known as microparticles) were measured in plasma with flow cytometry and labeled against glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). In addition, platelet EVs and their CD40 ligand expression were measured. Patients with SED had significantly higher concentrations of AQP4 and GFAP-positive EVs and EVs co-expressing AQP4/GFAP than patients with MDD and healthy controls. Patients with MDD had significantly higher concentrations of GFAP-positive EVs and EVs co-expressing AQP4/GFAP than healthy controls. Platelet EVs did not differ between groups. CD40 ligand expression was significantly higher in patients with SED and MDD than in controls. In conclusion, the present study suggests that patients with SED, and to some extent, patients with MDD, have increased leakage of astrocyte-derived EVs through the blood–brain barrier.https://doi.org/10.1038/s41598-021-81453-8
collection DOAJ
language English
format Article
sources DOAJ
author Johanna Wallensten
Anna Nager
Marie Åsberg
Kristian Borg
Aniella Beser
Alexander Wilczek
Fariborz Mobarrez
spellingShingle Johanna Wallensten
Anna Nager
Marie Åsberg
Kristian Borg
Aniella Beser
Alexander Wilczek
Fariborz Mobarrez
Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
Scientific Reports
author_facet Johanna Wallensten
Anna Nager
Marie Åsberg
Kristian Borg
Aniella Beser
Alexander Wilczek
Fariborz Mobarrez
author_sort Johanna Wallensten
title Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
title_short Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
title_full Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
title_fullStr Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
title_full_unstemmed Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
title_sort leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-01-01
description Abstract Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-derived EVs could be higher in patients with SED than in patients with major depressive disorder (MDD) and healthy controls. Patients with SED (n = 31), MDD (n = 31), and healthy matched controls (n = 61) were included. Astrocyte-derived EVs (previously known as microparticles) were measured in plasma with flow cytometry and labeled against glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). In addition, platelet EVs and their CD40 ligand expression were measured. Patients with SED had significantly higher concentrations of AQP4 and GFAP-positive EVs and EVs co-expressing AQP4/GFAP than patients with MDD and healthy controls. Patients with MDD had significantly higher concentrations of GFAP-positive EVs and EVs co-expressing AQP4/GFAP than healthy controls. Platelet EVs did not differ between groups. CD40 ligand expression was significantly higher in patients with SED and MDD than in controls. In conclusion, the present study suggests that patients with SED, and to some extent, patients with MDD, have increased leakage of astrocyte-derived EVs through the blood–brain barrier.
url https://doi.org/10.1038/s41598-021-81453-8
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