SR 57227对小鼠戊四氮诱发癫痫的抗惊厥作用。
The anticonvulsant effects of SR 57227 on pentylenetetrazole-induced seizure in mice.
作者信息
Li Bingjin, Wang Liang, Sun Zhihui, Zhou Yang, Shao Dongyuan, Zhao Jing, Song Yunong, Lv Jiayin, Dong Xue, Liu Changhong, Wang Pu, Zhang Xingyi, Cui Ranji
机构信息
Second hospital of Jilin University, Changchun, China; National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
出版信息
PLoS One. 2014 Apr 1;9(4):e93158. doi: 10.1371/journal.pone.0093158. eCollection 2014.
Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT3 receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4) of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT3 receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT3 receptor subtype is a potential target for the treatment of epilepsy.
最近，研究表明血清素在癫痫控制中起重要作用。然而，5-羟色胺受体亚型的具体作用尚未得到充分描述，尤其是5-羟色胺3型受体。本研究旨在探讨5-羟色胺3型受体在戊四氮（PTZ）诱导的小鼠癫痫发作中的作用。首先，5-羟色胺3型受体激动剂SR 57227以剂量依赖的方式显著延长了癫痫发作潜伏期。在PTZ处理的小鼠中，SR 57227也降低了癫痫发作评分和死亡率。此外，SR 57227的这些抗惊厥作用被5-羟色胺3型受体拮抗剂昂丹司琼抑制。然而，不同剂量的昂丹司琼单独对癫痫发作潜伏期、癫痫发作评分或死亡率没有影响。免疫组织化学研究还表明，PTZ处理的小鼠海马体（齿状回、CA1、CA3和CA4）中c-Fos表达显著增加。此外，在PTZ和SR 57227处理的小鼠中，昂丹司琼显著抑制了c-Fos表达。一项酶联免疫吸附测定研究表明，SR 57227减弱了PTZ诱导的海马体和皮质中γ-氨基丁酸水平的抑制作用，SR 57227的减弱作用在海马体中被昂丹司琼拮抗，但在皮质中未被拮抗。我们的研究结果表明，SR 57227激活5-羟色胺3型受体，这在PTZ诱导的癫痫发作控制中起重要作用，可能与海马体中的γ-氨基丁酸活性有关。因此，5-羟色胺3型受体亚型是治疗癫痫的潜在靶点。
Zotero 插件