Figure 1.

Representative measurements of oxygen consumption rates in mitochondria isolated from the cortex of 3xTg and age-matched control females at 2 months (A), 6 months (B) and 14 months of age (C), and males (D–F). Basal level of OCR was measured in the presence of Complex I substrates pyruvate and malate. Coupled respiration was measured after the addition of ADP (2 mM). Oligomycin (1 μM) was then added to terminate coupled respiration through inhibition of ATP synthase. The uncoupled respiration rate was determined by adding the uncoupling agent FCCP (4 μM) to remove the pH gradient and enable maximal rates of electron transport. The injection of rotenone (1 μM) and antimycin A (1 μM) blocked respiratory electron flux at complexes I and III (non-mitochondrial respiration rates). Calculated coupled respiration at state 3 and uncoupled respiration were significantly decreased (* p < 0.05) in cortical mitochondria of 3xTg female mice at 2, 6 and 14 months, and SRC was significantly reduced at 2 and 6 months (Table G, in bold). In 3xTg males, coupled respiration was significantly decreased at 6 and 14 months, and uncoupled respiration was down at 14 months (* p < 0.05). Data are expressed as OCR in pmoles/min, and values are expressed as mean ± SEM of n = 4–6 replicates.