Figure 6

Alpha-synuclein impairs basal mitochondrial respiration in PGC1α-KO neurons. Primary neuronal cultures were derived from the cerebral cortex of PGC1α-KO mice and co-transduced with either a non-coding AAV vector (NCV), an AAV vector encoding human aSyn, or with an AAV vector encoding PGC-1α (PGC1α). (a,b) Basal oxygen consumption was measured from individual cultures in the conditions NCV alone (n = 15), NCV + aSyn (n = 20), NCV + PGC1α (n = 19) and aSyn + PGC1α (n = 15). (a,d) Some of the individual cultures were treated with CCCP, in order to determine the percentage of spare respiratory capacity (d): NCV alone (n = 6), NCV + aSyn (n = 10), NCV + PGC1α (n = 4) and aSyn + PGC1α (n = 5). Other individual cultures were treated with oligomycin to determine (c) the oligomycin-resistant residual respiration and (e) the percentage of oxygen consumption used for ATP production: NCV alone (n = 9), NCV + aSyn (n = 10), NCV + PGC1α (n = 10) and aSyn + PGC1α (n = 10). Statistical analysis: two-way ANOVA with Newman-Keuls post-hoc test. (b-d): significant interaction between the aSyn and PGC1α effects, *p < 0.05; **p < 0.01; ***p < 0.001; (e): significant group effect of PGC1α, ***p < 0.001.