Neuronal conditional knockout of NRSF decreases vulnerability to seizures induced by pentylenetetrazol in mice.

Neuron restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor, has been reported to modulate neuronal excitability and acts as endogenous anticonvulsant in kainic acid-induced or kindling-evoked seizure activity. However, whether NRSF functions in pentylenetetrazol (PTZ)-induced seizure activity has never been studied. To investigate the role of endogenous NRSF in the epileptogenesis induced by PTZ, in our experiment, NRSF neuronal conditional knockout mice (NRSF cKO) were adopted, in which NRSF was specifically deleted in neurons by the Cre-loxP system. Seizure threshold for PTZ, including the dose-response convulsions and the threshold dose, was compared between NRSF cKO and control mice. The threshold dose of PTZ that induced clonic and tonic seizures was significantly higher in NRSF cKO mice compared with the control. Similarly, the median lethal dose (LD(50)) of PTZ in NRSF cKO mice was also considerably higher than that of the control mice. These results revealed that NRSF cKO mice are of higher resistance to convulsions induced by PTZ. Our work first demonstrated the function of NRSF in PTZ-induced seizure and provided new evidence for differential pathways in diverse types of seizure.