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The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis

[ Vol. 19 , Issue. 3 ]

Author(s):

Mahdi Goudarzvand, Yaser Panahi, Reza Yazdani, Hosein Miladi, Saeed Tahmasebi, Amin Sherafat, Sanaz Afraei, Kosar Abouhamzeh, Mahnaz Jamee, Kawthar Jasim Mohammad Rida Al-Hussieni, Hamed Mohammadi, Ali Mohebbi, Nikoo Hossein-Khannazer, Majid Zaki-Dizaji, Maria Maddalena Di Fiore, Antimo D'Aniello and Gholamreza Azizi*   Pages 316 - 325 ( 10 )

Abstract:


Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice.

Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits.

Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice.

Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage.

Keywords:

Experimental autoimmune encephalomyelitis, matrix metalloproteinase-2, D-aspartate, neurosteroids, TNF-α, IL-6, CCL-2.

Affiliation:

Department of Physiology and Pharmacology, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, North Khorasan University of Medical Sciences, Bojnurd, Research Centre for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Department of Pathology, Imam Khomeini Hospital affiliated to Social Security Organization, Arak, Department of Biology, Arak Branch, Islamic Azad University, Arak, Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Research Centre for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Student Research Committee, Alborz University of Medical Sciences, Alborz, Student Research Committee, Alborz University of Medical Sciences, Alborz, Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Growth and Development Research Centre, Paediatrics Centre of Excellence, Children’s Medical Centre, Tehran University of Medical Sciences, Tehran, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Universita della Campania "L. Vanvitelli" Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Via Vivaldi 43, 81100, Caserta, Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "L. Vanvitelli", via Vivaldi 43, 81100, Caserta, Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj

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