Research Paper Advance Articles

β-amyloid monomers drive up neuronal aerobic glycolysis in response to energy stressors

Inhibition of mitochondria-bound HK-1 by lonidamine prevented lactate production due to Aβ release. Neurons were glucose-starved for 2 hours before returning to 3 mM glucose. γ-Secretase inhibitor IX (γ-Sec Inh, 100 nM) reduced lactate release both in oligomycin-treated neurons (Oligo, 5 μg/ml for 1 hr) (A) and kainate-treated neurons (KA, 100 μM for 40 min) (B). The addition of synthetic Aβ42 monomers (mAβ, 100 nM) prevented the reduction of lactate release, induced by γ-Sec Inh, both in (A and B). Lonidamine (200 μM) reduced the rescuing effect of exogenous Aβ42 monomers in both cases (A and B). Bars represent the means ± SEM of 4 determinations. In (A) p *control (CTRL) or **Oligo in the absence of γ-Sec Inh, and p #Oligo + γ-Sec Inh or ##Oligo + γ-Sec Inh + mAβ. In (B) p *control (CTRL) or **KA in the absence of γ-Sec Inh or #KA + γ-Sec Inh, and p ##KA + γ-Sec Inh + mAβ; one-way ANOVA with post hoc Fisher LSD multiple comparison method.

Figure 7. Inhibition of mitochondria-bound HK-1 by lonidamine prevented lactate production due to Aβ release. Neurons were glucose-starved for 2 hours before returning to 3 mM glucose. γ-Secretase inhibitor IX (γ-Sec Inh, 100 nM) reduced lactate release both in oligomycin-treated neurons (Oligo, 5 μg/ml for 1 hr) (A) and kainate-treated neurons (KA, 100 μM for 40 min) (B). The addition of synthetic Aβ42 monomers (mAβ, 100 nM) prevented the reduction of lactate release, induced by γ-Sec Inh, both in (A and B). Lonidamine (200 μM) reduced the rescuing effect of exogenous Aβ42 monomers in both cases (A and B). Bars represent the means ± SEM of 4 determinations. In (A) p < 0.001 vs. *control (CTRL) or **Oligo in the absence of γ-Sec Inh, and p < 0.05 vs. #Oligo + γ-Sec Inh or ##Oligo + γ-Sec Inh + mAβ. In (B) p < 0.001 vs. *control (CTRL) or **KA in the absence of γ-Sec Inh or #KA + γ-Sec Inh, and p < 0.05 vs. ##KA + γ-Sec Inh + mAβ; one-way ANOVA with post hoc Fisher LSD multiple comparison method.