Clin Psychopharmacol Neurosci 2019; 17(2): 261-272  
Antidepressant-like Effects Induced by Chronic Blockade of the Purinergic 2X7 Receptor through Inhibition of Non-like Receptor Protein 1 Inflammasome in Chronic Unpredictable Mild Stress Model of Depression in Rats
Feyza Aricioglu1, Ceren Sahin Ozkartal1, Tugce Bastaskin1, Erdem Tüzün2, Cansu Kandemir3, Serap Sirvanci3, Cem Ismail Kucukali2, Tijen Utkan4
1Department of Pharmacology and Psychopharmacology Research Unit, Marmara University School of Pharmacy, 2Department of Neuroscience, Aziz Sancar Institute of Experimental Medical Research, Istanbul University, 3Department of Histology and Embryology, Marmara University School of Medicine, Istanbul, 4Department of Pharmacology, Kocaeli University School of Medicine, Kocaeli, Turkey
Correspondence to: Erdem Tüzün, MD, Department of Neuroscience, Aziz Sancar Institute of Experimental Medical Research, Istanbul University, Topkapı
Mahallesi, Vakıf Gureba Caddesi, Fatih 34390, Istanbul, Turkey
Tel: +90-212-4142000, Fax: +90-216-3452952, E-mail: drerdem@yahoo.com
ORCID: https://orcid.org/0000-0002-4483-0394
Received: June 7, 2018; Revised: July 11, 2018; Accepted: July 23, 2018; Published online: May 31, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: Purinergic 2X7 receptor (P2X7R) activation is known to be involved in pathogenesis of depression. Our aims were to investigate P2X7R-activated inflammasome pathways in parallel with induction of depression and to test the antidepressant-like effects of the selective P2X7R antagonist Brilliant Blue G (BBG) in a rat model of chronic unpredictable mild stress (CUMS).
Methods: Male Wistar albino rats were divided into control, CUMS, CUMS+BBG25 (25 mg/kg/day) and CUMS+BBG50 (50 mg/kg/day) groups (n=10 for each group). Various stressors were applied to rats for 6 weeks to establish the CUMS model and daily BBG treatment was started at the end of 3rd week. Sucrose preference test and forced swim test (FST) were performed to assess antidepressant-like effects. Brain samples were obtained for real-time polymerase chain reaction and immunohistochemistry analysis.
Results: In FST, duration of immobility was reduced in the CUMS+BBG50 group. Also, BBG treatment significantly enhanced sucrose preference. While NLRP3 gene expression levels were unchanged in rats exposed to the CUMS protocol, expression levels of other inflammasome pathway factors NLRP1, caspase-1, ASC, NF-B, IL-1, IL-6 and P2X7R were increased. BBG treatment reduced expression levels of these factors. Likewise, Iba-1 and GFAP immunoreactivities were enhanced by the CUMS protocol and this action was reversed by BBG treatment.
Conclusion: Chronic administration of BBG in CUMS model results in antidepressant-like activity in a dose dependent manner. Molecular and histological results show that these effects might be at least partially related to the suppression of inflammasome-related neuroinflammatory responses and suggest involvement of NLRP1 in depression.
Keywords: Depression; Coomassie Brilliant Blue; ATP receptor; Purinergic P2X7 receptors; Animal models.


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Funding Information
  • Scientific Research Project Unit of Marmara Üniversitesi
      10.13039/501100008386
      SAG-C-YLP-110915-0416
  • Scientific Research Project Unit of Marmara Üniversitesi
      10.13039/501100008386
      SAG-E-120613-0233
  • Scientific Research Projects Coordination Unit of Istanbul University
      10.13039/501100002657
      22790

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