Carnosine inhibits pentylenetetrazol-induced seizures by histaminergic mechanisms in histidine decarboxylase knock-out mice

Yuan Yuan Zhu, Zheng Bing Zhu-Ge, Deng Chang Wu, Shuang Wang, Lu Ying Liu, Hiroshi Ohtsu, Zhong Chen

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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 (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/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 (500 mg/kg) were time-dependent and reached a peak at 1 h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/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 (75 mg/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.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalNeuroscience Letters
Volume416
Issue number3
DOIs
Publication statusPublished - 2007 Apr 18

Keywords

  • Carnosine
  • Histamine
  • Histidine decarboxylase
  • Pentylenetetrazol
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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