Impact of the chronic administration of doxycycline on LID induced ROS and MMPs
Reactive oxygen species: 6-OHDA lesion and L-DOPA treatment increased ROS production as measured by fluorescence intensity (Figs. 4-D and -I) in the dopamine-denervated striatum. Co-administration of doxycycline (6-OHDA+chronic-doxycycline+L-DOPA) reduced the ROS fluorescence intensity (80% arbitrary units) (Figs. 4-E and -I). The ROS level was positively correlated with the dyskinesia severity (r=0.9; p<0.0001; Fig. 4-J).
Expression of MMP-2/MMP-9 activity : The activity of MMP-2/MMP-9 increased in the striatum of rats with 6-OHDA lesions (6-OHDA+chronic-vehicle+vehicle), and those with L-DOPA induced dyskinesia (6-OHDA+chronic-vehicle+L-DOPA Figs. 4-F, -G and -K). Doxycycline reduced MMP-2/MMP-9 activity in the 6-OHDA lesioned rats (6-OHDA+chronic-doxycycline+vehicle) and after L-DOPA induced dyskinesia (6-OHDA+chronic-doxycycline+L-DOPA p<0.0001, Figs. 4-H and -K). The activity of MMP-2/MMP-9 exhibited a positive correlation with dyskinesia (r=0.7, p<0.0001, Fig. 4-L).
MMP-2 and MMP-9 gel zymography: There was an increase in the MMP-2 and MMP-9 in the striatum of rats with 6-OHDA lesion (6-OHDA+chronic-vehicle+vehicle), without statistical significance. Doxycycline treatment per se slightly decreased MMP-2 and MMP-9 detection. The MMP-9 increase reached statistical significance following L-DOPA treatment (6-OHDA+chronic-vehicle+L-DOPA; p<0.0001, Supplementary Figs. 4-B and -D). Doxycycline co-treatment significantly reduced MMP-2 and MMP-9 detection after LID expression (6-OHDA+chronic-doxycycline+L-DOPA).