Expression of fructose-1,6-bisphosphatase 1 is associated with [18F]FDG uptake and prognosis in patients with mesial temporal lobe epilepsy

Abstract

Objectives: To determine whether fructose-1,6-bisphosphatase 1 (FBP1) expression is associated with [¹⁸F]FDG PET uptake and postsurgical outcomes in patients with mesial temporal lobe epilepsy (mTLE) and to investigate whether the molecular mechanism involving gamma-aminobutyric acid type A receptor (GABA_AR), glucose transporter-3 (GLUT-3), and hexokinase-II (HK-II).

Methods: Forty-three patients with mTLE underwent [¹⁸F]FDG PET/CT. Patients were divided into Ia (Engel class Ia) and non-Ia (Engel class Ib-IV) groups according to more than 1 year of follow-up after surgery. The maximum standard uptake value (SUV_max) and asymmetry index (AI) of hippocampus were measured. The relationship among the SUV_max, AI, prognosis, and FBP1 expression was analyzed. A lithium-pilocarpine acute mTLE rat model was subjected to [¹⁸F]FDG micro-PET/CT. Hippocampal SUV_max and FBP1, GABA_AR, GLUT-3, and HK-II expression were analyzed.

Results: SUV_max was higher in the Ia group than in the non-Ia group (7.31 ± 0.97 vs. 6.56 ± 0.96, p < 0.05) and FBP1 expression was lower in the Ia group (0.24 ± 0.03 vs. 0.27 ± 0.03, p < 0.01). FBP1 expression was negatively associated with SUV_max and AI (p < 0.01). In mTLE rats, the hippocampal FBP1 increased (0.26 ± 0.00 vs. 0.17 ± 0.00, p < 0.0001), and SUV_max, GLUT-3 and GABA_AR levels decreased significantly (0.73 ± 0.12 vs. 1.46 ± 0.23, 0.20 ± 0.01 vs. 0.32 ± 0.05, 0.26 ± 0.02 vs. 0.35 ± 0.02, p < 0.05); no significant difference in HK-II levels was observed. In mTLE patients and rats, FBP1 negatively correlated with SUV_max and GLUT-3 and GABA_AR levels (p < 0.05).

Conclusion: FBP1 expression was inversely associated with SUV_max in mTLE, which might inhibit [¹⁸F]FDG uptake by regulating GLUT-3 expression. High FBP1 expression was indicative of low GABA_AR expression and poor prognosis.

Key points: • It is of paramount importance to explore the deep pathophysiological mechanisms underlying the pathogenesis of mesial temporal lobe epilepsy and find potential therapeutic targets. • [¹⁸F]FDG PET has demonstrated low metabolism in epileptic regions during the interictal period, and hypometabolism may be associated with prognosis, but the pathomechanism of this association remains uncertain. • Our results support the possibility that FBP1 might be simultaneously involved in the regulation of glucose metabolism levels and the excitability of neurons and suggest that targeting FBP1 may be a viable strategy in the diagnosis and treatment of mesial temporal lobe epilepsy.

Keywords: Epilepsy, temporal lobe; Fluorodeoxyglucose F18; Fructose-bisphosphatase; Positron emission tomography; Receptors, GABA-A.