[Effect of LINGO-1 gene silencing on movement function of EAE mice]

To explore the effect of LINGO-1 silencing on movement function of experimental autoimmune encephalomyelitis (EAE) mice.

EAE was established by induction of MOG35-55 in female C57/BL6 mice. Then female EAE mice (n=105) were completely randomly divided into 5 groups: group A (n=21): 5 µl 5×10(9) Tu/ml lentiviral vectors encoding LINGO-1shRNA (LV/LINGO-1-shRNA) by intracerebroventricular (ICV) injection, group B (n=21): 5 µl 5×10(8)Tu/ml LV/LINGO-1-shRNA by ICV injection, group C (n=21): 5 µl 5×10(7) Tu/ml LV/LINGO-1-shRNA by ICV injection, group D (n=21): 5 µl LVCON053 by ICV injection and group E (n=21): untreated.The movement function was scored and the expression of LINGO-1 protein was detected by Western blot on day 1, 3, 7, 14, 21, 30 after ICV among different groups. Luxol fast blue staining was performed to know about conditions of myelin sheath on day 30.

The expression of LINGO-1 in EAE mouse was obviously downregulated ever since day 7 after LV/LINGO-1-shRNA implantation.Group B and C achieved the most reduction of LINGO-1 expression (1.99±0.13, 2.08±0.10, P<0.05, P<0.01). Simultaneously, the movement functional score of group A, B and C was lowered at different levels from day 7 (3.11±0.13, 2.42±0.13, 2.96±0.10 vs 3.56±0.15, 3.87±0.12, P<0.01, P<0.01, P<0.05), with the most marked decrease in group B. The densities of myelin sheaths in group A and B were higher than untreated group on day 30 (0.72±0.09, 0.83±0.11 vs 0.56±0.10, P<0.05, P<0.01).

LV/LINGO-1shRNA by ICV injection is an effective method to silence LINGO-1 expression. LINGO-1 silencing could ameliorate motor function and promote formation of myelin sheaths. But the effects do not enhance with the increase of LV/LINGO-1-shRNA dose.