Time course and spatial profile of Nogo-A expression in experimental autoimmune encephalomyelitis in C57BL/6 mice.
Title | Time course and spatial profile of Nogo-A expression in experimental autoimmune encephalomyelitis in C57BL/6 mice. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Theotokis, P., Lourbopoulos A., Touloumi O., Lagoudaki R., Kofidou E., Nousiopoulou E., Poulatsidou K-N., Kesidou E., Tascos N., Spandou E., & Grigoriadis N. |
Journal | J Neuropathol Exp Neurol |
Volume | 71 |
Issue | 10 |
Pagination | 907-20 |
Date Published | 2012 Oct |
ISSN | 1554-6578 |
Keywords | Acute Disease, Animals, Encephalomyelitis, Autoimmune, Experimental, Female, Gene Expression Regulation, GPI-Linked Proteins, Mice, Mice, Inbred C57BL, Myelin Proteins, Neurons, Oligodendroglia, Receptors, Cell Surface, Time Factors |
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. |
DOI | 10.1097/NEN.0b013e31826caebe |
Alternate Journal | J. Neuropathol. Exp. Neurol. |
PubMed ID | 22964785 |