Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat

Giacinto Bagetta, Anna Maria Paoletti, Aida Leta, Claudio Del Duca, Robert Nisticò, D. Rotiroti, M. Tiziana Corasaniti

Research output: Contribution to journalArticle

Abstract

Administration of tacrine (5 mg/kg ip), an anticho-linesterase agent, in rats pretreated (24 h beforehand) with lithium chloride (LiCl; 12 mEq/kg ip) provides a useful experimental model to study limbic seizures and delayed hippocampal damage. Here we report Western blotting evidence demonstrating that in rat LiCl and tacrine enhance the expression of neuronal nitric oxide synthase (nNOS), but not eNOS, enzyme protein in the hippocampus during the preconvulsive period and this triggers seizures and hippocampal damage. In fact, systemic administration of 7-nitro indazole (7-NI; 50 mg/kg given ip 30 min before tacrine), a selective inhibitor of nNOS, prevented the expression of motor and electrocortical (ECoG) seizures and abolished neuronal cell death in the hippocampus. A lower dose (5 mg/kg ip) of 7-NI was ineffective. In conclusion, the present data support a role for abnormal nNOS expression in the mechanism which triggers limbic seizures and delayed excitotoxic damage in the hippocampus of rat.

Original languageEnglish
Pages (from-to)255-260
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume291
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • 7-nitro indazole
  • ENOS
  • LiCl
  • Neuronal death
  • NNOS
  • NO
  • Seizures
  • Tacrine

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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