title: Role of orexin-A in experimental autoimmune encephalomyelitis.
abstract: The aim of this study was to evaluate the effects of orexin-A (OX-A) on behavioral and pathological parameters and on gene expression of some multiple sclerosis-related peptides in a model of experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous administration of MOG 35-55. Following immunization, the treatment was initiated by using SB.334867 (orexin-1 receptor antagonist) and/or OX-A. Locomotor activity and exploratory behaviors were monitored using open field and T-maze continuous alternation task (T-CAT) respectively. Pain sensitivity was assessed by hot-plate test. Histopathological assessments were performed by H&E staining. The expression of TGF-β, MBP, MMP-9, IL-12, iNOS and MCP-1 were measured using real-time PCR method in lumbar spinal cord. OX-A administration in EAE mice remarkably attenuated the clinical symptoms, increased latency response in hot plate test, inhibited infiltration of inflammatory cells, up-regulated mRNA expression of TGF-β as well as MBP and down-regulated mRNA expression of iNOS, MMP-9 and IL-12. In contrast SB.334867 administration in EAE mice deteriorated the clinical symptoms, decreased the alternation in T-CAT, increased infiltration of inflammatory cells, down-regulated mRNA expression of TGF-β and MBP and up-regulated mRNA expression of iNOS. Results of this study suggest that the orexinergic system might be involved in pathological development of EAE. These findings suggest orexinergic system as a potential target for treatment of multiple sclerosis.
authors: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors: Iman
authors: I
authors: Fatemi
authors: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors: Ali
authors: A
authors: Shamsizadeh
authors: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors: Fatemeh
authors: F
authors: Ayoobi
authors: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors: Zahra
authors: Z
authors: Taghipour
authors: Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
authors: Mohammad Hossein
authors: MH
authors: Sanati
authors: Pharmacutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Ali
authors: A
authors: Roohbakhsh
authors: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: motevalian.m@iums.ac.ir.
authors: Manijeh
authors: M
authors: Motevalian
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001583:Benzoxazoles / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009287:Naphthyridines; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000068796:Orexin Receptor Antagonists / Q000627:therapeutic use; D000068797:Orexins / Q000378:metabolism* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D016207:Cytokines; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D000068797:Orexins; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D014508:Urea; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9
keywords: C57BL/6 mice; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Orexin-A; SB.334867