Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat.
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
Giacinto
G
Department of Pharmacobiology, University of Calabria, Arcavacata di Rende (CS), Italy. gbagett@tin.it
Paoletti
Anna Maria
AM
Leta
Aida
A
Del Duca
Claudio
C
Nisticò
Robert
R
Rotiroti
D
D
Corasaniti
M Tiziana
MT
D000818:Animals; D015153:Blotting, Western; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D007191:Indazoles / Q000494:pharmacology; D018021:Lithium Chloride / Q000037:antagonists & inhibitors; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D013619:Tacrine / Q000037:antagonists & inhibitors
D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D007191:Indazoles; D018696:Neuroprotective Agents; D013619:Tacrine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D018021:Lithium Chloride; C080122:7-nitroindazole