Fig. 3: shRNA knockdown of endogenous VMAT2 results in degeneration in the substantia nigra.

a Representative montage image of the SN immunolabeled for TH following unilateral AAV2-shVMAT2 transduction. b The number of TH-positive neuronal counts from the transduced hemisphere were compared to the internal control nontransduced contralateral hemisphere. Each data point represents the total number of TH-positive neurons in the SNpc of each hemisphere of an individual animal calculated from serial sections throughout the SN. Counts in males receiving unilateral AAV2-shVMAT2 (left) (paired t-test, n = 5 animals, p = 0.0177), females that received unilateral AAV2-shVMAT2 (middle) (paired t-test, n = 5 animals, p = 0.0046), and males receiving unilateral AAV2-shControl (right) (paired t-test, n = 5 animals, n.s.). c Postural instability test was performed 20 weeks post-transduction in animals with AAV2-shVMAT2 and contralateral AAV2-shControl injections. Contralateral paw refers to the paw contralateral to and therefore affected by the AAV2-shVMAT2 injection (paired t-test, n = 4 animals, p < 0.0001). Each data point represents the average distance to trigger for each forepaw in an individual calculated over three trials. d Cylinder test was performed at 20 weeks post-transduction in animals with AAV2-shVMAT2 and contralateral AAV2-shControl injections. The number of paw touches were counted during rearing behavior from three 5-min trials (paired t-test, n = 4 animals, p = 0.0301). Each data point represents the number of paw touches for each paw in an individual animal summed over 3 5-min trials. Error bars represent mean and standard error of the mean.