FIGURE 1.

Clinical features of EAE in WT, α7KO, or α9KO mice after nicotine treatment. Mice were immunized with MOG_35–55 and treated with nicotine for up to 16 d via osmotic pumps, and disease severity was scored each day as described in Materials and Methods. (A) Disease progression was significantly altered in WT-EAE-Nic (black lines with squares, n = 14) compared with WT-EAE-PBS (black lines with circles, n = 17) from days 8 to 15. (B) Clinical scores were not different between α7KO-EAE-PBS (green line with black circles, n = 11) and nicotine-treated α7KO (α7KO-EAE-Nic, green line with green diamond, n = 11) mice, nor between α7KO EAE (PBS-treated and nicotine-treated combined) and WT-EAE-PBS mice (black line). (C) Although there were no differences between α9KO-EAE-PBS (red line with black circles, n = 20) and nicotine-treated α9KO (α9KO-EAE-Nic, red line with red diamond, n = 20) mice, disease progression was significantly lower in α9KO mice, irrespective of drug treatment, compared with WT-EAE-PBS mice. (D and E) Average clinical scores from days 13 to 16 (D) and cumulative clinical scores from disease onset to day 16 (E) were reduced by nicotine treatment (patterned bars) in WT mice (black and white bars), but not in α7KO (green bars) or α9KO (red bars) mice. Again, both these parameters were significantly lower in α9KO mice compared with their WT counterparts, regardless of drug treatment. (F) Disease onset was also delayed in WT-EAE-Nic mice, whereas no drug or genetic effects were observed in α7KO or α9KO mice. These data confirm previous findings that nicotine is protective against EAE, that both α7 and α9 nAChRs appear to be involved in these protective effects. In addition, our data support the hypothesis that the α9 nAChR may play a role in endogenous immune-regulatory mechanisms. Asterisk denotes a statistically significant difference between groups (Mann–Whitney U test, *p < 0.05).