*3.3. CY-09 Increased Cerebral Glucose Metabolism in 3*×*Tg-AD Mice*

Next, we evaluated the effect of NLRP3 inflammasome activation on cerebral glucose metabolism using static and dynamic PET. 18F-FDG is the most commonly used PET tracer for glucose metabolism. As an analog of glucose, 18F-FDG is transported into cells by GLUTs from blood after the i.v. injection and is then phosphorylated by HK. Due to the differences in structure, 6-P-18F-FDG cannot be catalyzed by glucose-6-phosphate isomerase and must remain in the cytoplasm. The amount and distribution of 6-P-18F-FDG represent the glucose metabolism levels in different brain regions.

Static PET results are shown in Figure 2a–e; compared with NTg mice, the standard uptake values (SUVs) of the whole brain, the cortex, and the hippocampus were greatly decreased in 3×Tg-AD mice, with the *p*-value lower than 0.05. After CY-09 treatment, the SUVs were significantly higher in 3×Tg-AD mice than those in non-treated AD mice, with a *p*-value lower than 0.05. There were no differences in the weight of the mice in the four groups. Consistent with the static PET results, the cerebral SUVs of NTg and CY-09 treated 3×Tg-AD mice were also higher than those of the 3×Tg-AD mice, even though the SUVs of the four groups of mice increased in dynamic PET over time (Figure 2f–h). Moreover, the results of the cerebral metabolic rate of glucose (CMRglu) showed a notable reduction in the 3×Tg-AD mice and a remarkable increase in the CY-09 treated 3×Tg-AD mice, with the *p*-values all lower than 0.05. Overall, the PET data demonstrated that inhibiting NLRP3 inflammasome activation helps to restore cerebral glucose metabolism in the 3×Tg-AD mice.
