Figure 7.
NADH and dopamine accumulation underlie hypersensitivity of Ndufs4−/− neurons to rotenone. Mesencephalic neurons were cultured from individual E14 Ndufs4+/+ and Ndufs4−/− embryos. (A) Deletion of the Ndufs4 gene increases basal intracellular NADH content. (B) 8-h 10-nM rotenone–induced intracellular dopamine accumulation is significantly higher in Ndufs4−/− cultures than in Ndufs4+/+ cultures. (C) 10 nM taxol inhibits 8-h 10-nM rotenone–induced dopamine accumulation in both Ndufs4+/+ and Ndufs4−/− cultures. (D) Pretreatment with 0.2-mM α-methyl-ρ-tyrosine (AMPT) protects dopamine neurons cultured from both Ndufs4+/+ and Ndufs4−/− embryos against 5-nM rotenone toxicity for 24 h. Data are means ± SEM. n = 3–4; *, P < 0.05; **, P < 0.01.