Carnosine inhibits pentylenetetrazol-induced seizures by histaminergic mechanisms in histidine decarboxylase knock-out mice
Carnosine inhibits pentylenetetrazol-induced seizures by histaminergic mechanisms in histidine decarboxylase knock-out mice
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DOI：
10.1016/j.neulet.2007.01.075
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发表时间：
2007-04
影响因子：
2.5
通讯作者：
Yuan-yuan Zhu;Zheng-bing Zhu-Ge;Deng-chang Wu;Shuang Wang;Lu-ying Liu;H. Ohtsu;Zhong Chen
中科院分区：
文献类型：
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作者：
Yuan-yuan Zhu;Zheng-bing Zhu-Ge;Deng-chang Wu;Shuang Wang;Lu-ying Liu;H. Ohtsu;Zhong Chen
In the present study, we used both histidine decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500mg/kg) were time-dependent and reached a peak at 1h. However, it had no significant effect on HDC-KO mice. Carnosine (500mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that α-fluoromethylhistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine–histidine–histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future.
