Fig. 7

Increased GSK3β activity in the brain tissues leads to hypersusceptibility to drug-induced seizure in Wwox knockout mice. a Wwox^−/− mice showed increased susceptibility to seizure induction by the injection of pilocarpine (50 mg/kg), a muscarinic receptor agonist. Behavioral scoring of seizure severity according to the Racine’s scale [55] in three genotypes of mice for 60 min is presented. b Higher seizure activity was observed in Wwox^−/− mice after injection of PTZ (30 mg/kg), a GABAergic receptor antagonist, as compared with Wwox^+/+ and Wwox^+/− mice. Pretreatment of ethosuximide (ETS, 150 mg/kg) suppressed PTZ-induced seizure activity in Wwox^−/− mice. c Increased activation of GSK3β was determined in the cerebellum, hippocampus and cerebral cortex of Wwox^−/− mice at postnatal day 20, as evidenced by dephosphorylation of GSK3β at Ser9. β-actin was used as an internal control in western blotting. Quantitative densitometry of the immunoblots was performed, and the numbers depict the ratio of phosphorylated or total GSK3β to β-actin protein level in the brain tissues. The representative results of four independent experiments are shown. d Pretreatment of a GSK3β inhibitor LiCl (60 mg/kg) suppressed PTZ-induced seizure activity in Wwox^−/− mice. The results are expressed as means ± SEM. n.s., non-significant. ***P < 0.001