title: Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats.
abstract: 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 recognized 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, occluding, 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, 1-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.
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Petra
authors.initials: P
authors.lastname: Sántha
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Hoyk
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Mészáros
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Fruzsina R
authors.initials: FR
authors.lastname: Walter
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Tóth
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Lóránd
authors.initials: L
authors.lastname: Kiss
authors.affiliation: Biomolecular Electronics Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Kincses
authors.affiliation: Department of Psychiatry, Alzheimer's Disease Research Centre, University of Szeged Szeged, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Oláh
authors.affiliation: Department of Medical Biology, University of Szeged Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Seprényi
authors.affiliation: Department of Biotechnology, University of Szeged Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Rákhely
authors.affiliation: Biomolecular Electronics Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Dér
authors.affiliation: Department of Psychiatry, Alzheimer's Disease Research Centre, University of Szeged Szeged, Hungary.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.affiliation: Department of Psychiatry, Alzheimer's Disease Research Centre, University of Szeged Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
authors.affiliation: Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kittel
authors.affiliation: Biological Barriers Research Group, Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
keywords: GFAP; blood-brain barrier; brain capillary ultrastructure; brain endothelial cell; glial endfeet; glucose-transporter-1; restraint stress; tight junction
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