Administration of tacrine (5 mg/kg ip), an anticholinesterase 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.

Bagetta, G., Paoletti, A., Leta, A., Del Duca, C., Nistico', R.g., Rotiroti, D., et al. (2002). Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 291(2), 255-260 [10.1006/bbrc.2002.6424].

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

BAGETTA, GIACINTO;NISTICO', ROBERT GIOVANNI;CORASANITI, MARIA TIZIANA
2002

Abstract

Administration of tacrine (5 mg/kg ip), an anticholinesterase 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14
English
Animals; Blotting, Western; Cholinesterase Inhibitors; Enzyme Inhibitors; Hippocampus; Indazoles; Lithium Chloride; Male; Neuroprotective Agents; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Rats; Rats, Wistar; Seizures; Tacrine
Bagetta, G., Paoletti, A., Leta, A., Del Duca, C., Nistico', R.g., Rotiroti, D., et al. (2002). Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 291(2), 255-260 [10.1006/bbrc.2002.6424].
Bagetta, G; Paoletti, A; Leta, A; Del Duca, C; Nistico', Rg; Rotiroti, D; Corasaniti, Mt
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/133234
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