Mechanism of epileptic seizures in the neuron-specific adaptor protein complex type 3B knockout mice / 中华神经科杂志

ABSTRACT

Objective To explore the mechanism of spontaneous seizures in adaptor protein complex type 3B knockout mice(AP3M2KO mice).Methods AP3M2KO mice were generated.Seizures and electroencephalogram(EEG)were monitored using video camera and telemetry system.Glutamate and GABA releases were determined using in vivo microdialysis method.Results AP3M2KO mice began to suffer from spontaneous seizures 8 weeks after the birth,but did not show any other behavior abnormality.The onset of ictal discharge over the temporal region was synchronized with seizures.There were no significant differences in basal glutamate and GABA releases in hippocampus between AP3M2KO((0.35±0.08)pmol/20μl and(2.94±1.69)fmol/20μl,respectively)and wild-type mice.However,the 50 mmol/L K+-evoked GABA release was impaired in AP3M2KO mice((63.5±11.8)fmol/20μl vs(209.2±63.7)fmol/20 μl,t=4.405,P＜0.05),whereas no significant difference was found in K+-evoked glutamate release.Conclusions AP3M2KO mice suffer from epileptic seizures similar to the clinical features of human epilepsy.The impairment of inhibitory GABAergic transmission iS involved in the mechanism of spontaneous seizures in AP3M2KO mice.