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).