Lingo-1 Inhibited by RNA Interference Promotes Functional Recovery of Experimental Autoimmune Encephalomyelitis
Article first published online: 17 JUL 2014
© 2014 Wiley Periodicals, Inc.
The Anatomical Record
Volume 297, Issue 12, pages 2356–2363, December 2014
How to Cite
Wang, C.-J., Qu, C.-Q., Zhang, J., Fu, P.-C., Guo, S.-G. and Tang, R.-H. (2014), Lingo-1 Inhibited by RNA Interference Promotes Functional Recovery of Experimental Autoimmune Encephalomyelitis. Anat Rec, 297: 2356–2363. doi: 10.1002/ar.22988
- Issue published online: 17 NOV 2014
- Article first published online: 17 JUL 2014
- Manuscript Accepted: 7 MAY 2014
- Manuscript Received: 19 FEB 2014
- RNA interference;
- experimental autoimmune encephalomyelitis
Lingo-1 is a negative regulator of myelination. Repairment of demyelinating diseases, such as multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), requires activation of the myelination program. In this study, we observed the effect of RNA interference on Lingo-1 expression, and the impact of Lingo-1 suppression on functional recovery and myelination/remyelination in EAE mice. Lentiviral vectors encoding Lingo-1 short hairpin RNA (LV/Lingo-1-shRNA) were constructed to inhibit Lingo-1 expression. LV/Lingo-1-shRNA of different titers were transferred into myelin oligodendrocyte glycoprotein-induced EAE mice by intracerebroventricular (ICV) injection. Meanwhile, lentiviral vectors carrying nonsense gene sequence (LVCON053) were used as negative control. The Lingo-1 expression was detected and locomotor function was evaluated at different time points (on days 1,3,7,14,21, and 30 after ICV injection). Myelination was investigated by luxol fast blue (LFB) staining.LV/Lingo-1-shRNA administration via ICV injection could efficiently down-regulate the Lingo-1 mRNA and protein expression in EAE mice on days 7,14,21, and 30 (P < 0.01), especially in the 5 × 108 TU/mL and 5 × 109 TU/mL LV/Lingo-1-shRNA groups. The locomotor function score in the LV/Lingo-1-shRNA treated groups were significantly lower than the untreated or LVCON053 group from day 7 on. The 5 × 108 TU/mL LV/Lingo-1-shRNA group achieved the best functional improvement (0.87 ± 0.11 vs. 3.05 ± 0.13, P < 0.001). Enhanced myelination/remyelination was observed in the 5 × 107, 5 × 108, 5 × 109 TU/mL LV/Lingo-1-shRNA groups by LFB staining (P < 0.05, P < 0.01, and P < 0.05).The data showed that administering LV/Lingo-1-shRNA by ICV injection could efficiently knockdown Lingo-1 expression in vivo, improve functional recovery and enhance myelination/remyelination. Antagonism of Lingo-1 by RNA interference is, therefore, a promising approach for the treatment of demyelinating diseases, such as MS/EAE. Anat Rec, 297:2356–2363, 2014. © 2014 Wiley Periodicals, Inc.