These data are a composite of three separate studies. … Shown in Figure ​Figure22 are the changes in different measures of motor Trametinib behavior as a composite of two of the three studies following motor behavior from week 1 to 11. The inset to the right shows data from the original pilots study (n = 4 per

group) that only followed motor activity from week 3 to 7. The height of the bar graphs in this inset is the median score for each measure with the minimum and maximum shown above. A two-way repeated measures ANOVA for a 11-week study showed a significant difference between the total distance traveled and the number of rearing postures at week 7 between Inhibitors,research,lifescience,medical vehicle (n = 8) and rotenone (n = 6) treated animals. This would suggest a trend toward hypokinesia with rotenone treatment. Figure 2 Motor behavior. Shown are the changes in different measures of motor behavior over a 11-week period as a composite of two of Inhibitors,research,lifescience,medical the three studies following motor behavior from week 1 to 11. The inset to the right shows data from the original pilots study … Immunostaining for TH in the midbrain and striatum

at week 11 postvehicle and rotenone treatment are shown in Figure ​Figure3.3. There is a substantial decrease in TH staining in both the substantia nigra pars compacta (SNpc) the location of DA neurons and the DA fibers in the underlying substantia nigra pars reticularis (SNpr). By week Inhibitors,research,lifescience,medical 11 there is a ca. 25% reduction in TH staining in the SNpc as shown in Figure ​Figure4.4. This reduction in TH staining is also accompanied

by a 10–15% reduction Inhibitors,research,lifescience,medical in neuronal numbers in the SNpc as shown in Figure ​Figure55. Figure 3 Site-specific reduction in tyrosine hydroxylase staining. Shown are representative micrographs at different magnifications of immunostaining for tyrosine hydroxylase (brown) at week 11 postvehicle or rotenone treatment. Inhibitors,research,lifescience,medical The upper two panels show immunostaining … Figure 4 Reduction in tyrosine hydroxylase in the substantia nigra compacta. The bar graphs show the mean percent of control for vehicle (n = 4) and rotenone treated animals (n = 4) sampled from the substantia nigra compacta areas depicted in the micrographs below. … Figure 5 Reduction in neuron density in the substantia nigra compacta. The top panels show representative green immunofluorescence staining for the neuron’s specific of neuN protein in the substantia nigra compacta (SNC) 11 weeks postvehicle and rotenone treatments. … Accompanying the loss of DA neurons in the SNpc are cellular signs of neuroinflammation, oxidative stress and protein misfolding. Shown in Figure ​Figure66 are photomicrographs of immunostaining for activated microglia in rotenone treated animals as compared to control. There is a threefold increase in the number neuroinflammatory microglia in the SNpc 11 weeks postrotenone treatment.