Time Course and Spatial Profile of Nogo-A Expression in Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice

Autor: Evangelia Spandou, Evangelia Kesidou, Kyriaki-Nepheli Poulatsidou, Olga Touloumi, Evangelia Nousiopoulou, Roza Lagoudaki, Nikolaos Grigoriadis, Paschalis Theotokis, Evangelia Kofidou, Athanasios Lourbopoulos, Nikolaos Tascos
Rok vydání: 2012
Předmět:
Zdroj: Journal of Neuropathology & Experimental Neurology. 71:907-920
ISSN: 1554-6578
0022-3069
DOI: 10.1097/nen.0b013e31826caebe
Popis: 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.
Databáze: OpenAIRE