TY - JOUR
T1 - Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat
AU - Bagetta, Giacinto
AU - Paoletti, Anna Maria
AU - Leta, Aida
AU - Del Duca, Claudio
AU - Nisticò, Robert
AU - Rotiroti, D.
AU - Corasaniti, M. Tiziana
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - 7-nitro indazole
KW - ENOS
KW - LiCl
KW - Neuronal death
KW - NNOS
KW - NO
KW - Seizures
KW - Tacrine
UR - http://www.scopus.com/inward/record.url?scp=0036293870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036293870&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2002.6424
DO - 10.1006/bbrc.2002.6424
M3 - Article
C2 - 11846398
AN - SCOPUS:0036293870
VL - 291
SP - 255
EP - 260
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -