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. 2011 Oct 12;31(41):14508–14520. doi: 10.1523/JNEUROSCI.1560-11.2011

Figure 4.

Figure 4.

Topical application of ALP inhibitor Bafilomycin A1 leads to elevated levels of LC3II and p62 and increased α-synuclein levels in vivo depending on the preexisting synuclein burden. A, B, Immunoblot levels of autophagosome marker LC3II and macroautophagy substrate p62 in homogenates of cortex of nontransgenic, human α-synuclein transgenic, and α-synuclein-GFP transgenic mice treated with autophagy inhibitor Bafilomycin A1 (2.5 μm; 24 h) or vehicle. Non-tg: LC3II: 0.17 ± 0.03, n = 8 (vehicle), 0.46 ± 0.04, n = 4 (BafA1); t test, p = 0.0004; p62: 0.83 ± 0.16, n = 8 (vehicle), 1.54 ± 0.06, n = 4 (BafA1); t test, p = 0.01; (h)αSyn tg: LC3II: 0.15 ± 0.05, n = 8 (vehicle), 1.09 ± 0.19, n = 4 (BafA1); t test, p < 0.0001; p62: 0.67 ± 0.05, n = 9 (vehicle), 1.35 ± 0.11, n = 4 (BafA1); t test, p < 0.0001; αSyn-GFP tg: LC3II: 0.29 ± 0.03, n = 3 (vehicle), 0.48 ± 0.06, n = 3 (BafA1); t test, p = 0.04; p62: 0.38 ± 0.06, n = 3 (vehicle), 1.08 ± 0.07, n = 3 (BafA1); t test, p = 0.0017. C–F, Immunoblot levels of α-synuclein in homogenates of recovered cortical tissue of nontransgenic, human α-synuclein transgenic, and α-synuclein-GFP transgenic mice after treatment with ALP inhibitor BafA1 (2.5 μm; 24 h), HCQ (100 μm; 24 h), or vehicle. Non-tg: 0.43 ± 0.03, n = 17 (vehicle), 0.33 ± 0.02, n = 10 (BafA1); ANOVA, p < 0.0001; Dunnett's posttest, p > 0.05, not significant; (h)αSyn tg: 0.42 ± 0.05, n = 15 (vehicle), 0.90 ± 0.08, n = 7 (BafA1), 1.44 ± 0.01, n = 2 (HCQ); ANOVA, p = 0.0001; Dunnett's posttest, p < 0.01; αSyn-GFP tg: αSyn-GFP: 0.25 ± 0.04, n = 11 (vehicle), 0.69 ± 0.04, n = 3 (BafA1); ANOVA, p < 0.0001; Dunnett's posttest, p < 0.01; endogenous α-synuclein: 0.25 ± 0.05, n = 11 (vehicle), 0.21 ± 0.02, n = 3 (BafA1); ANOVA, p < 0.0001; Dunnett's posttest, p > 0.05, not significant. *p < 0.05, **p < 0.01, ***p < 0.001 compared with vehicle-treated littermates. Error bars indicate SEM.