05; F5,24=20.77, p<0.0001; Fig. 2b) and the ST (p≤0.001; F5,24=285.5, p<0.0001; Fig. 2c). hSNCA

mRNA levels also are reduced in ST injected with AAV-hSNCA and AAV-mir30-SNCA compared to those injected with AAV-hSNCA and AAV-NS (p≤0.001, F5,24=285.5, p<0.0001; Fig. Stem Cell Compound Library 2c). However, hSNCA RNA levels in ventral midbrain injected with AAV-hSNCA and AAV-mir30-SNCA do not differ from those in ventral midbrain injected with AAV-hSNCA and AAV-NS. These data suggest that hSNCA mRNA and vector DNA, in the case of injection of AAV-hSNCA alone, are transported to the ST. To examine effects of hSNCA expression and silencing in the SN on motor behavior, forelimb behavior was examined using the cylinder test 1 and 2 months after unilateral SN injection of AAV-hSNCA, AAV-hSNCA and AAV-mir30-SNCA or AAV-hSNCA and AAV-NS (Fig. 3). As expected, a preference for ipsilateral forelimb use and a deficit in contralateral forelimb use was observed in rats expressing hSNCA (i.e., rats injected with AAV-hSNCA alone or AAV-hSNCA and AAV-NS) at both 1 month (hSNCA: p≤0.01, ipsi-77.9±4.2%, contra-21.1±3.9%, n=16; hSNCA and NS: p≤0.01, ipsi-69.3±3.1%, contra-26.4±2.0%, BIBW2992 cell line n=15; F4,132=11.78, p<0.0001) and 2 months (hSNCA: p≤0.05, ipsi-77.5±6.2%, contra-22.5±6.2%, n=11; hSNCA and NS: p≤0.05, ipsi-80.0±3.1%, contra-18.8±3.3%, n=10; F4,87=18.69,

p<0.0001) after injection. hSNCA gene silencing with mir30-SNCA results in protection against the hSNCA-induced

deficit in forelimb use by 2 months after injection, when ipsilateral and contralateral forelimb use does not statistically differ (ipsi-51.1±2.1%, contra-45.3±1.1%, n=11), although a preference selleck chemical (p≤0.05) for ipsilateral forelimb use (57.3±3.1%,n=16) and a deficit in contralateral forelimb use (37.3±2.8%) was observed at 1 month in rats where hSNCA was silenced with mir30-SNCA. The 2-way ANOVA showed no significant effect of time or interaction of time and treatment. SN brain sections from rats injected with AAV-hSNCA, AAV-hSNCA and AAV-mir30-SNCA or AAV-hSNCA and AAV-NS at 1 and 2 months survivals were stained for TH-IR. Qualitatively, SNs injected with AAV-hSNCA and AAV-NS have the most evident reduction in TH-IR, where TH-IR neurons were observed in smaller, narrower bands, at both survivals (Fig. S4a and Fig. 4a), compared with the other treatments. TH-IR neurons throughout the entire SN were counted using unbiased stereology at both 1 and 2 months (Fig. S4b and Fig. 4b). At 1 month, TH-IR neurons are reduced in hSNCA-expressing SN, (hSNCA: 8521±538, p≤0.01, n=5, and hSNCA and NS: 7557±642, p≤0.001, n=5) compared to the respective control SN (hSNCA: 12,116±290, n=5, and hSNCA+NS: 12,415±377, n=5), but are not significantly different in SN where hSNCA is silenced using mir30-SNCA (10,118±1290, n=5) compared to control SN (12,679±251, n=5; F5,24=10.72, p<0.