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Cited by 55Barrier Structure and Function StudiesSchizophrenia research and treatmentTryptophan and brain disorders

Early Loss of Blood-Brain Barrier Integrity Precedes NOX2 Elevation in the Prefrontal Cortex of an Animal Model of Psychosis

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Schiavone, Stefania, Mhillaj, Emanuela, Neri, Margherita, Morgese, Maria Grazia, Tucci, Paolo, Bove, Maria, Valentino, Mario, Di Giovanni, Giuseppe +4 more·2017·Molecular Neurobiology
DOI 10.1007/s12035-016-9791-8PMC PMC5355521
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Abstract

The social isolation rearing of young adult rats is a model of psychosocial stress and provides a nonpharmacological tool to study alterations reminiscent of symptoms seen in psychosis. We have previously demonstrated that social isolation in rats leads to increased oxidative stress and to cerebral NOX2 elevations. Here, we investigated early alterations in mRNA expression leading to increased NOX2 in the brain. Rats were exposed to a short period of social isolation (1 week) and real-time polymerase chain reaction (PCR) for mRNA expression of genes involved in blood-brain barrier (BBB) formation and integrity (ORLs, Vof 21 and Vof 16, Leng8, Vnr1, and Trank 1 genes) was performed. Real-time PCR experiments, immunohistochemistry, and Western blotting analysis showed an increased expression of these genes and related proteins in isolated rats with respect to control animals. The expression of specific markers of BBB integrity, such as matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), occludin 1, and plasmalemmal vesicle associated protein-1 (PV-1), was also significantly altered after 1 week of social isolation. BBB permeability, evaluated by quantification of Evans blue dye extravasation, as well as interstitial fluid, was significantly increased in rats isolated for 1 week with respect to controls. Isolation-induced BBB disruption was also accompanied by a significant increase of Interleukin 6 (IL-6) expression. Conversely, no differences in NOX2 levels were detected at this time point. Our study demonstrates that BBB disruption precedes NOX2 elevations in the brain. These results provide new insights in the interplay of mechanisms linking psychosocial stress to early oxidative stress in the brain, disruption of the BBB, and the development of mental disorders.

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  • BBB impairment occurs early in the mouse model of chronic sleep deprivation and the rat model of social isolation.

    “Additionally, BBB impairment also occurs early in the mouse model of chronic sleep deprivation (241) and the rat model of social isolation (524).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [524]

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Cited by

Sorted by citations

Authors
Schiavone, S., Mhillaj, E., Neri, M., Morgese, M. G., Tucci, P., Bove, M., Valentino, M., Di Giovanni, G., Pomara, C., Turillazzi, E., Trabace, L., & Cuomo, V.
Affiliations
  • University of Foggia (IT)
  • Sapienza University of Rome (IT)
  • University of Malta (MT)
Corresponding author
Trabace, Luigia
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2016-02-24
Volume
54
Issue
3
Pages
2031-2044
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-016-9791-8
PMC
PMC5355521
OpenAlex
W2286982470
Cited by
55
References
5
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 3
FWCI
3.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurobiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • OAR@UM (University of Malta) (submittedVersion, other-oa)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc)
Funders
  • Pro.Ali.Fun. (Pro.Ali.Fun. Project 2011 to LT)
  • Apulia Region (FIR 2015-2018, FIR 2015-2018 to MGM)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
blood-brain barrier integrity, NOX2, NADPH oxidase, social isolation, psychosocial stress, psychosis, oxidative stress, prefrontal cortex, blood-brain barrier permeability, matrix metalloproteinases, occludin, interleukin-6, gene expression, animal models of psychosis
MeSH terms
NADPH Oxidase 2, Animals, Blood-Brain Barrier, Disease Models, Animal, Female, Male, Psychotic Disorders, Social Isolation, Rats, Wistar, Prefrontal Cortex, Rats

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