a, Schematic of the experimental schedule for 6-OHDA-induced lesion in substantia nigra (SN) followed by AAV-shPTB treatment and behavioral tests.
b, 6-OHDA-induced unilateral loss of TH+ cells in midbrain (top, Scale bar: 500 μm), accompanied with increased GFAP+ astrocytes (bottom, Scale bar: 50 μm).
c, Comparison between unlesioned (top) and 6-OHDA-lesioned nigra (middle), showing converted DA neurons (yellow) after AAV-shPTB treatment (bottom). Scale bar: 50 μm.
d,e, TH+ fibers in striatum treated with AAV-Empty (top) or AAV-shPTB (bottom) (d). Scale bar: 500 μm. Amplified views from (d), showing extensive RFP+TH+ fibers (e). Scale bar: 10 μm. (b) to (e) were each based on 3 independently repeated experiments with similar results.
f,g, Quantified DA neuron cell bodies (f) or fibers (g) in the unlesioned side (blue), remaining endogenous RFP–TH+ DA neurons in the lesioned side (green), and converted RFP+TH+ DA neurons in the lesioned side (orange). Data were from two sets of mice (n=3 in each set) transduced with AAV-shPTB or AAV-Empty.
h,i, Quantification of RFP+ (h) or RFP+TH+ (i) fiber density in different subbrain regions, as indicated at bottom (n=3 mice in each group).
Statistical significance from panel (f) to (i) was determined by ANOVA with post-hoc Tukey test and represented as mean+/− SEM. NS: not significant. Specific P-values are indicated in each panel.