Investigation of blood-brain barrier disruption in an animal model of mania induced by D-amphetamine

Luiza Paul Géa; Bianca Wollenhaupt-Aguiar; Devon Watts; William Maich; Flavio Kapczinski; Roohie Sharma; Ram Mishra; Adriane Ribeiro Rosa; Benicio N. Frey

Journal of Affective Disorders Reports (Jul 2022)

Investigation of blood-brain barrier disruption in an animal model of mania induced by D-amphetamine

Luiza Paul Géa,
Bianca Wollenhaupt-Aguiar,
Devon Watts,
William Maich,
Flavio Kapczinski,
Roohie Sharma,
Ram Mishra,
Adriane Ribeiro Rosa,
Benicio N. Frey

Affiliations

Luiza Paul Géa: Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500, Porto Alegre, RS, Brazil; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil; Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada
Bianca Wollenhaupt-Aguiar: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada
Devon Watts: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada; Neuroscience Graduate Program, McMaster University, 1280 Main Street West, Hamilton, ON, Canada
William Maich: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada; Mood Disorders Program, St. Joseph's Healthcare Hamilton, 100 West 5th Street, Hamilton, ON, Canada
Flavio Kapczinski: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada; Neuroscience Graduate Program, McMaster University, 1280 Main Street West, Hamilton, ON, Canada; Mood Disorders Program, St. Joseph's Healthcare Hamilton, 100 West 5th Street, Hamilton, ON, Canada
Roohie Sharma: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada
Ram Mishra: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada; Neuroscience Graduate Program, McMaster University, 1280 Main Street West, Hamilton, ON, Canada
Adriane Ribeiro Rosa: Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500, Porto Alegre, RS, Brazil; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil
Benicio N. Frey: Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, Canada; Neuroscience Graduate Program, McMaster University, 1280 Main Street West, Hamilton, ON, Canada; Mood Disorders Program, St. Joseph's Healthcare Hamilton, 100 West 5th Street, Hamilton, ON, Canada; Corresponding author.

Journal volume & issue: Vol. 9
p. 100368

Abstract

Read online

Background: High levels of inflammation and oxidative stress are observed in bipolar disorder (BD) being further associated with mood symptoms and cognitive dysfunction. Due to the crosstalk between the periphery and central nervous system, the blood-brain barrier (BBB) disruption has been considered a key mechanism of the BD pathophysiology. This study aimed to evaluate claudin-5 expression in the brain of a model of mania induced by D-amphetamine (AMPH). Methods: Wistar rats were injected with AMPH (2 mg/kg i.p.) and treated with lithium (47.5 mg/kg i.p.). Locomotor behavior was assessed, followed by euthanasia, blood collection, and brain removal. Tumor necrosis factor (TNF) α and thiobarbituric acid reactive substances (TBARS) were quantified in the serum and brain tissue, and claudin-5 was quantified in the brain. Results: AMPH-injected animals exhibited increased locomotor activity. In the serum, TBARS levels were augmented in lithium-treated groups, while TNFα was not detected. In the brain, TBARS and TNFα did not differ between groups but were positively andstrongly correlated in the striatum of AMPH-injected rats. Contrary to our hypothesis, AMPH and lithium injections did not affect claudin-5 levels in the brain. Limitations: The main limitations include the lack of a dynamic marker of BBB integrity and limited number of biomarkers analyzed. Conclusions: This is one of the first attempts to investigate the effects of AMPH on BBB integrity, and no disruption was observed. Still, we provide rationale for future research to elucidate the importance of BBB disruption in BD, recently proposed as a marker of illness progression.

Published in Journal of Affective Disorders Reports

ISSN: 2666-9153 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Other systems of medicine: Mental healing
Website: https://www.journals.elsevier.com/journal-of-affective-disorders-reports

About the journal

Abstract

Keywords