Behavior and outcome after CDNF treatment in PFF-injected mice and rats
(A–E) Mouse behavior and TH optical density after injections to 3-month-old mice. (A) Cylinder test at 1 month after PFF injection, before CDNF treatment, n = 8/group. (B) Cylinder test at 3 months after PFF/PBS injection, 2 months after CDNF/PBS. The graph represents ipsilateral, contralateral, as well as both paw touches on the cylinder wall. PFF + PBS/PFF + CDNF indicates that PFFs were given at day 0 and PBS/CDNF was given 1 month later, n = 8/group. p = 0.0051 (C) TH optical density in the striatum as a percentage of the control side at 1 month after PFF injection, n = 8. (D) TH optical density in the striatum as a percentage of the control side 3 months after PFFs. PFF only indicates PFFs given at day 0, and PFF + PBS/CDNF PFFs given at day 0 and PBS/CDNF 1 month later, n = 8/group. (E) TH optical density in the striatum as a percentage of the control side. PBS/PFF only indicates PBS or PFFs given at day 0 and no other injections, PBS + PBS indicates PBS given at day 0 and again 1 month later, PFF + PBS/CDNF indicates fibrils at day 0 and PBS/CDNF 1 month later, n = 4–7/group. (F–H) Mouse behavior after injections to 1-year-old mice. (F) Rotarod 1 month after PBS (control, n = 10) or PFF injections (n = 30). (G) Coat hanger time 1 month after injection, PBS (n = 9); PFF (n = 30). p = 0.022. (H) Coat hanger time 3 months after PBS or PFFs injection, 2 months after PBS or CDNF. PBS/PFF only indicates PBS or PFFs given at day 0 and no other injections, PBS + PBS indicates PBS given at day 0 and again 1 month later, PFF + PBS/CDNF indicates fibrils at day 0 and PBS/CDNF 1 month later, n = 10/group. p = 0.0410. (I and J) Behavior and histopathological outcome after injections to 1-year-old rats. (I) Contralateral paw use (percent of total paw use). Baseline indicates the data obtained before PFFs were injected, 1 month is 1 month after fibrils but before installation of minipumps, and 4 months is 4 months after fibrils and 3 months after treatment. Minipumps administer PBS (white symbols), CDNF at 1.5 μg/day (gray symbols), or 3.0 μg/day (black symbols) to the striatum for 30 days, n = 9–12/group. p = 0.0114. (J) Number of inclusions of α-synuclein phosphorylated at S129 (p-aSyn) in the substantia nigra for each treatment 4 months after fibril injections, n = 10–12/group. Error bars represent SEM.