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. 2021 Jan 5;24(1):101979. doi: 10.1016/j.isci.2020.101979

Figure 2.

Figure 2

Neuronal expression of the glucose transporter hGlut3 attenuates the age-related reduction in ATP concentration in brain neuron and glycolytic gene expression

(A) Glucose concentration in head lysates decreased during aging. The glucose concentrations in 5-, 30- and 50-day-old fly heads, normalized to protein concentration, are shown (mean ± SE, n = 6; ∗p < 0.05; one-way ANOVA, followed by Tukey's HSD multiple comparisons test).

(B) dGlut1 mRNA expression decreased in fly heads during aging. qRT-PCR was performed using RNA extracted from the heads of 5- and 30-day-old flies (mean ± SE, n = 3; ∗∗p < 0.01; Student's t-test).

(C) The expression of glycolytic genes decreased in the fly brain during aging. The mRNA expression of genes encoding glycolytic enzymes in the heads of 5- and 30-day-old flies was quantified using qRT-PCR (mean ± SE, n = 3; ∗∗p < 0.01, ∗∗∗p < 0.001; Student's t-test).

(D) Neuronal knockdown of Pfk, which encodes a rate-limiting glycolytic enzyme, reduced ATP concentration in 3-day-old fly neurons (mean ± SE, n = 9–12; ∗∗∗p < 0.001; Student's t-test).

(E) The age-related reduction in ATP concentration in neuronal cell bodies was not identified in Pfk-deficient neurons. The expression of ATeam and Pfk RNAi was driven by the pan-neuronal driver elav-GAL4. The 5-day-old and 50-day-old flies were subjected to imaging analyzes at the same time. The experiments were repeated with timely independent cohorts of flies obtained from different crosses to analyze more than 12 brains for each age. Data are mean ± SE; n.s., p > 0.05, ∗p < 0.05; Student's t-test.

(F and G) Neuronal expression of hGlut3 ameliorates the age-related reduction in ATP concentration and glycolytic gene expression and the decline in physical function. (F) ATP concentration did not decrease with aging in neurons overexpressing hGlut3. Expression of ATeam and hGlut3 was driven by the pan-neuronal driver elav-GAL4. The 5-day-old and 50-day-old flies were subjected to imaging analyzes at the same time. The experiments were repeated with timely independent cohorts of flies obtained from different crosses to analyze more than 12 brains for each age. (mean ± SE; n.s., p > 0.05; Student's t-test). (G) Neuronal expression of hGlut3 attenuated the age-associated decline in glycolytic gene expression. The mRNA expression of genes encoding key glycolytic enzymes was quantified using qRT-PCR in the heads of 5- and 30-day-old flies. Flies carrying the driver alone were used as controls. Data are mean ± SE, n = 3; n.s., p > 0.05, ∗p < 0.05, ∗∗p < 0.01; one-way ANOVA, followed by Tukey's HSD multiple comparisons test.