PMID- 30289086 OWN - NLM STAT- MEDLINE DCOM- 20190828 LR - 20190828 IS - 2212-3873 (Electronic) IS - 1871-5303 (Linking) VI - 19 IP - 3 DP - 2019 TI - The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis. PG - 316-325 LID - 10.2174/1871530318666181005093459 [doi] AB - 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, 17beta-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 17beta-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. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Goudarzvand, Mahdi AU - Goudarzvand M AD - Department of Physiology and Pharmacology, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran. FAU - Panahi, Yaser AU - Panahi Y AD - North Khorasan University of Medical Sciences, Bojnurd, Iran. FAU - Yazdani, Reza AU - Yazdani R AD - Research Centre for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran. FAU - Miladi, Hosein AU - Miladi H AD - Department of Pathology, Imam Khomeini Hospital affiliated to Social Security Organization, Arak, Iran. FAU - Tahmasebi, Saeed AU - Tahmasebi S AD - Department of Biology, Arak Branch, Islamic Azad University, Arak, Iran. FAU - Sherafat, Amin AU - Sherafat A AD - Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, United States. FAU - Afraei, Sanaz AU - Afraei S AD - Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. FAU - Abouhamzeh, Kosar AU - Abouhamzeh K AD - Research Centre for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran. FAU - Jamee, Mahnaz AU - Jamee M AD - Student Research Committee, Alborz University of Medical Sciences, Alborz, Iran. FAU - Al-Hussieni, Kawthar Jasim Mohammad Rida AU - Al-Hussieni KJMR AD - Student Research Committee, Alborz University of Medical Sciences, Alborz, Iran. FAU - Mohammadi, Hamed AU - Mohammadi H AD - Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. AD - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Mohebbi, Ali AU - Mohebbi A AD - Growth and Development Research Centre, Paediatrics Centre of Excellence, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hossein-Khannazer, Nikoo AU - Hossein-Khannazer N AD - Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Zaki-Dizaji, Majid AU - Zaki-Dizaji M AD - Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Di Fiore, Maria Maddalena AU - Di Fiore MM AD - Universita della Campania "L. Vanvitelli" Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Via Vivaldi 43, 81100, Caserta, Italy. FAU - D'Aniello, Antimo AU - D'Aniello A AD - Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "L. Vanvitelli", via Vivaldi 43, 81100, Caserta, Italy. FAU - Azizi, Gholamreza AU - Azizi G AD - Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. AD - Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. LA - eng PT - Journal Article PL - United Arab Emirates TA - Endocr Metab Immune Disord Drug Targets JT - Endocrine, metabolic & immune disorders drug targets JID - 101269157 RN - 0 (Inflammation Mediators) RN - 0 (Neurotransmitter Agents) RN - 4SR0Q8YD1X (D-Aspartic Acid) SB - IM MH - Animals MH - Brain/drug effects/metabolism/pathology MH - D-Aspartic Acid/*administration & dosage MH - Encephalomyelitis, Autoimmune, Experimental/*blood/*drug therapy/pathology MH - Female MH - Inflammation Mediators/*blood MH - Mice MH - Mice, Inbred C57BL MH - Neurotransmitter Agents/*blood OTO - NOTNLM OT - CCL-2 OT - D-aspartate OT - Experimental autoimmune encephalomyelitis OT - IL-6 OT - TNF-alpha OT - matrix metalloproteinase-2 OT - neurosteroids. EDAT- 2018/10/06 06:00 MHDA- 2019/08/29 06:00 CRDT- 2018/10/06 06:00 PHST- 2018/04/20 00:00 [received] PHST- 2018/07/18 00:00 [revised] PHST- 2018/08/03 00:00 [accepted] PHST- 2018/10/06 06:00 [pubmed] PHST- 2019/08/29 06:00 [medline] PHST- 2018/10/06 06:00 [entrez] AID - EMIDDT-EPUB-93445 [pii] AID - 10.2174/1871530318666181005093459 [doi] PST - ppublish SO - Endocr Metab Immune Disord Drug Targets. 2019;19(3):316-325. doi: 10.2174/1871530318666181005093459.