The role of methyl‑CpG binding domain 3 in seizures and epileptogenesis

Abstract

Methyl‑CpG binding domain protein 3 (Mbd3), a component of the NuRD chromatin remodeling complex, plays a role in transcriptional regulation and has been implicated in neuronal development; however, its role in epilepsy remains unclear. This study investigated the effects of Mbd3 downregulation on seizure susceptibility and behavior in rats, using adeno‑associated viral vectors that code for short hairpin RNA to downregulate Mbd3 expression in the basolateral amygdala. Behavioral assessments included the open field test, elevated plus maze test, and hyperexcitability test. Seizure susceptibility was evaluated using the PTZ challenge and PTZ kindling models. A decreased Mbd3 level significantly increased latency to seizure onset in the PTZ challenge, indicating a raised seizure threshold. Rats with reduced Mbd3 expression also exhibited increased anxiety‑like behavior in the open‑field test. Mbd3 downregulation did not affect the progression of epileptogenesis in the PTZ kindling model. These findings suggest that Mbd3 contributes to acute seizure susceptibility and emotional behavior but not to the long‑term development of epilepsy, highlighting its potential as an epigenetic modulator in seizure regulation.