Neurosteroid-Sensitive δ-GABA_A Receptors: A Role in Epileptogenesis?

The study investigated the role of neurosteroid-sensitive δ-GABA_A receptors (δ-GABARs) in epileptogenesis using a rat model of status epilepticus (SE). It found that δ-GABAR expression was down-regulated before the onset of epilepsy, while γ2 subunit expression increased after seizure onset. Inhibition of neurosteroid synthesis accelerated epileptogenesis, whereas blocking NMDA receptors during SE preserved δ-GABAR expression and prevented spontaneous seizures. These findings suggested that δ-GABARs and neurosteroids played a significant role in the development of epilepsy, with NMDA receptor activation during SE being crucial for δ-GABAR plasticity and the progression to epilepsy.