Figure 3.

Parkin^−/− mice display increased vulnerability to nigral DA neuron loss induced by repeated low-dose systemic LPS. A, Unbiased stereological analysis indicates that parkin−/− mice exposed to 3 months of low-dose systemic LPS followed by a 3 month wait and mice exposed to 6 months of low-dose systemic LPS display a significant reduction of TH-immunopositive neurons in the SNpc. The loss of TH-positive neurons in parkin−/− mice is reflected in the loss of NeuN-immunopositive neurons, confirming true neuronal loss. B, Unbiased stereological analysis indicates no loss of TH-positive or NeuN-positive neurons in the VTA in any of the groups. In A and B, error bars represent SEM, and the number of mice in each group is denoted in parentheses (n). Asterisks indicate significant differences compared with wild-type, saline-treated animals by three-way ANOVA followed by Tukey's HSD post hoc test at α = 0.05. C, Images of TH (purple) and NeuN (brown) immunohistochemistry from single coronal sections of wild-type mice in the 6 month treatment group compared with the parkin−/− mice in each of the exposure groups. The black arrowhead in high-magnification inset indicates a double-labeled TH/NeuN-immunopositive neuron, and the white arrowhead indicates a NeuN-only (nondopaminergic) neuron. Scale bars: low-magnification panels, 400 μm; high-magnification inset, 10 μm.