PT - JOURNAL ARTICLE AU - Rao, Wanqian AU - Tang, Yongxiang AU - Chen, Bei AU - Xiang, Shijun AU - Xiao, Ling AU - Zhu, Haoyue AU - Zhu, Zehua AU - Hu, Shuo TI - <strong>Fructose-1,6-Bisphosphatase 1 reduces 18F-FDG Uptake in an animal model of acute epilepsy: a possible mechanism for drug-resistant epilepsy?</strong> DP - 2022 Aug 01 TA - Journal of Nuclear Medicine PG - 2958--2958 VI - 63 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/63/supplement_2/2958.short 4100 - http://jnm.snmjournals.org/content/63/supplement_2/2958.full SO - J Nucl Med2022 Aug 01; 63 AB - 2958 Introduction: Despite the development of new antiepileptic drugs (AEDs), ~30% of people with epilepsy remain refractory to treatment and are said to have drug-resistant epilepsy (DRE), possibly for the unclear pathogenesis of DRE. Interictal 18F-FDG PET showed decreased glucose metabolism of the nervous in epileptic foci and regulating glucose metabolism can control seizures, both suggesting that glucose metabolic pathway may be one of pathogeneses of epilepsy. Studies have shown that fructose-1,6-bisphosphatase 1 (FBP1) is a key enzyme in the glycolysis pathway and may be associated with SUVmax in 18F-FDG PET imaging. Therefore, we will determine whether FBP1 expression is associated with, gamma-aminobutyric acid type A receptor (GABAAR), an inhibitory neurotransmitter receptor, and whether it is associated with 18F-FDG PET uptake, glucose transporter-3 (GLUT-3) and hexokinase-II (HK-II) expression in rats with epilepsy.Methods: The rats (6-8 weeks) were intraperitoneally (IP) injected with LiCl (127 mg/kg) and pilocarpine (40 mg/kg) to induce status epilepticus (SE), the control group was given LiCl but not pilocarpine. A modified Racine scale was used to evaluate seizure severity. The criterion of SE in this study was that recurrent seizures greater than or equal to Racine stage 4 lasted for 30min. At 30 minutes after seizure onset, only rats arriving SE were treated with diazepam (10 mg/kg) to terminate seizures, otherwise, they were excluded from the experiment. All rats underwent 18F-FDG micro-PET imaging on the third day after modeling. The max standard uptake value (SUVmax) of lesions was measured by sketching a volume of interest (VOI) in the hippocampus region, along with SUV ratio (SUVr) between VOI and cerebellum. After 18F-FDG micro-PET imaging, the rats were sacrificed. Immunohistochemistry staining and western blotting analysis were performed to measure the expression level of FBP1, GABAAR, GLUT-3 and HK-II.Results: The immunohistochemistry staining and western blotting results revealed that FBP1 was upregulated (both P&lt; 0.005) and GABAAR was downregulated (both P&lt; 0.05) in the epilepsy rats. There was an inverse relationship between FBP1 expression and GABAAR (r= -0.9286, P&lt; 0.0001). There was also an inverse relationship between FBP1 expression and SUVr (r= -0.8972, P&lt; 0.0001). FBP1 overexpression in epilepsy rats led to a significant decrease in GLUT-3 expression (both P&lt; 0.05). There was no significant difference between the control group and the experimental group in HK-II, either by immunohistochemistry staining or western blotting.Conclusions: SUVr was lower in rats with epilepsy than in normal rats, which could be the result of higher FBP1 expression in the former. FBP1 expression in rats with epilepsy was inversely associated with SUVr, and it was inversely associated with GABAAR and GLUT-3 expression. Decreasing FBP1 may be expected to provide a new idea for the treatment of DRE.