title: Time course and spatial profile of Nogo-A expression in experimental autoimmune encephalomyelitis in C57BL/6 mice.
abstract: Inhibition of the myelin-associated neurite outgrowth inhibitor Nogo-A has been found to be beneficial in experimental autoimmune encephalomyelitis (EAE), but there are little data on its expression dynamics during the disease course. We analyzed Nogo-A mRNA and protein during the course of EAE in 27 C57BL/6 mice and in 8 controls. Histopathologic and molecular analyses were performed on Day 0 (naive), preclinical (Day 10), acute (Days 18-22) and chronic (Day 50) time points. In situ hybridization and real-time polymerase chain reaction analyses revealed reduced Nogo-A mRNA expression at preclinical (p < 0.0001) and acute phases (p < 0.0001), followed by upregulation during the chronic phase (p < 0.0001). Nogo-A mRNA was expressed in neurons and oligodendrocytes. By immunohistochemistry and Western blot, there was increased Nogo-A protein expression (p < 0.001) in the chronic phase. Moreover, spatial differences were observed within EAE lesions. The pattern of Nogo-A protein expression inversely correlated with axonal regeneration growth-associated protein 43-positive axons (60% of which were Nogo-A contact-free during the acute phase) and axonal injury (β-amyloid precursor protein-positive axons). Cortical Nogo-66 receptor protein and mRNA levels increased during the chronic phase. The results indicate that Nogo-A and Nogo receptor are actively regulated in EAE lesions; this may indicate a specific time window for localized axonal regeneration in the acute phase of EAE.
authors.affiliation: B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Thessaloniki, Macedonia, Greece.
authors.forename: Paschalis
authors.initials: P
authors.lastname: Theotokis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Lourbopoulos
authors.forename: Olga
authors.initials: O
authors.lastname: Touloumi
authors.forename: Roza
authors.initials: R
authors.lastname: Lagoudaki
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kofidou
authors.forename: Evangelia
authors.initials: E
authors.lastname: Nousiopoulou
authors.forename: Kyriaki-Nepheli
authors.initials: KN
authors.lastname: Poulatsidou
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kesidou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tascos
authors.forename: Evangelia
authors.initials: E
authors.lastname: Spandou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
mesh_terms: D000208:Acute Disease; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D009836:Oligodendroglia / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse