Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Acta Biochim Biophys Sin (Shanghai). 2012 Jun;44(6):476-82. doi: 10.1093/abbs/gms023. Epub 2012 Apr 2.
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.
神经元限制沉默因子（NRSF），也称为抑制元件-1沉默转录因子，据报道可调节神经元兴奋性，并在红藻氨酸诱导或点燃诱发的癫痫发作活动中作为内源性抗惊厥药。然而，NRSF 是否在戊四氮（PTZ）诱导的癫痫发作活动中发挥作用尚未得到研究。为了研究内源性 NRSF 在 PTZ 诱导的癫痫发生中的作用，在我们的实验中，采用了 NRSF 神经元条件性敲除小鼠（NRSF cKO），其中 NRSF 通过 Cre-loxP 系统特异性缺失神经元。比较了 NRSF cKO 和对照组小鼠对 PTZ 的癫痫发作阈值，包括剂量反应性惊厥和阈值剂量。与对照组相比，NRSF cKO 小鼠的 PTZ 致阵挛和强直发作的阈值剂量显著升高。同样，NRSF cKO 小鼠的戊四氮半数致死剂量（LD（50））也明显高于对照组。这些结果表明，NRSF cKO 小鼠对 PTZ 诱导的惊厥具有更高的抵抗力。我们的工作首次证明了 NRSF 在 PTZ 诱导的癫痫发作中的作用，并为不同类型的癫痫发作中的差异途径提供了新的证据。
