Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been li...

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Main Authors: Petra eSántha, Szilvia eVeszelka, Zsófia eHoyk, Mária eMészáros, Fruzsina R. Walter, Andrea E. Tóth, Lóránd eKiss, András eKincses, Zita eOláh, György eSeprényi, Gabor eRakhely, András eDér, Magdolna ePákáski, Janos eKalman, Ágnes eKittel, Maria A Deli
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-01-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00088/full
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author Petra eSántha
Szilvia eVeszelka
Zsófia eHoyk
Mária eMészáros
Fruzsina R. Walter
Andrea E. Tóth
Lóránd eKiss
András eKincses
Zita eOláh
György eSeprényi
Gabor eRakhely
András eDér
Magdolna ePákáski
Janos eKalman
Ágnes eKittel
Maria A Deli
author_facet Petra eSántha
Szilvia eVeszelka
Zsófia eHoyk
Mária eMészáros
Fruzsina R. Walter
Andrea E. Tóth
Lóránd eKiss
András eKincses
Zita eOláh
György eSeprényi
Gabor eRakhely
András eDér
Magdolna ePákáski
Janos eKalman
Ágnes eKittel
Maria A Deli
author_sort Petra eSántha
collection DOAJ
description Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and behavioral dysfunctions.
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spelling doaj.art-35f85297c70f4cb9a49a2ab6c6dc88722022-12-22T02:02:19ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992016-01-01810.3389/fnmol.2015.00088173311Restraint stress-induced morphological changes at the blood-brain barrier in adult ratsPetra eSántha0Szilvia eVeszelka1Zsófia eHoyk2Mária eMészáros3Fruzsina R. Walter4Andrea E. Tóth5Lóránd eKiss6András eKincses7Zita eOláh8György eSeprényi9Gabor eRakhely10András eDér11Magdolna ePákáski12Janos eKalman13Ágnes eKittel14Maria A Deli15Biological Research Centre, HASBiological Research Centre, HASBiological Research Centre, HASBiological Research Centre, HASBiological Research Centre, HASBiological Research Centre, HASBiological Research Centre, HASBiological Research Centre, HASUniversity of SzegedUniversity of SzegedUniversity of SzegedBiological Research Centre, HASUniversity of SzegedUniversity of SzegedInstitute of Experimental Medicine, HASBiological Research Centre, HASStress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and behavioral dysfunctions.http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00088/fullBlood-Brain Barrierbrain endothelial cellGFAPtight junctionOccludinClaudin-5
spellingShingle Petra eSántha
Szilvia eVeszelka
Zsófia eHoyk
Mária eMészáros
Fruzsina R. Walter
Andrea E. Tóth
Lóránd eKiss
András eKincses
Zita eOláh
György eSeprényi
Gabor eRakhely
András eDér
Magdolna ePákáski
Janos eKalman
Ágnes eKittel
Maria A Deli
Restraint stress-induced morphological changes at the blood-brain barrier in adult rats
Frontiers in Molecular Neuroscience
Blood-Brain Barrier
brain endothelial cell
GFAP
tight junction
Occludin
Claudin-5
title Restraint stress-induced morphological changes at the blood-brain barrier in adult rats
title_full Restraint stress-induced morphological changes at the blood-brain barrier in adult rats
title_fullStr Restraint stress-induced morphological changes at the blood-brain barrier in adult rats
title_full_unstemmed Restraint stress-induced morphological changes at the blood-brain barrier in adult rats
title_short Restraint stress-induced morphological changes at the blood-brain barrier in adult rats
title_sort restraint stress induced morphological changes at the blood brain barrier in adult rats
topic Blood-Brain Barrier
brain endothelial cell
GFAP
tight junction
Occludin
Claudin-5
url http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00088/full
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