sb-334867-a and myelin-oligodendrocyte-glycoprotein-(35-55)

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.

Topics: Animals; Attention; Avoidance Learning; Benzoxazoles; Body Weight; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Exploratory Behavior; Female; Matrix Metalloproteinase 9; Maze Learning; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Myelin-Oligodendrocyte Glycoprotein; Naphthyridines; Nitric Oxide Synthase Type II; Orexin Receptor Antagonists; Orexins; Peptide Fragments; Severity of Illness Index; Spinal Cord; Time Factors; Urea