Role of nitric oxide in the epileptogenesis of EL mice.
OBJECTIVE
To understand the role of nitric oxide (NO) in the regulation of seizures, we measured the extracellular levels of the NO metabolites nitrite and nitrate as indices of NO generation in the parietal cortex, hippocampus, and temporal cortex of EL mice. Furthermore, alterations of neuronal, endothelial, and inducible nitric oxide synthetase (nNOS, eNOS, and iNOS, respectively) were observed to correlate them with epileptogenesis.


METHODS
EL mice of 20 weeks and 30 weeks of age (before and after the establishment of epileptogenesis, respectively) were used. Nitrite was quantified using the specific absorbancy of diazo dye. NOS isoenzymes (nNOS, iNOS, and eNOS) were also investigated in the hippocampus during development until mice were 30 weeks old. Samples (total protein, 8.33 to 8.43 microg) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by immunoblotting.


RESULTS
EL mice that experienced repetitive seizures showed a remarkable increase in nitrite in the hippocampus at 30 weeks of age compared with EL mice that had no experience of seizures. nNOS and iNOS were major and minor components, respectively, and both increased in parallel with the development of epileptogenesis. eNOS was not detectable.


CONCLUSIONS
Excess iNOS (and subsequent increase in harmful NO) and deficient eNOS (and subsequent decrease in NO identified as an endothelium-derived relaxing factor) may work together to form a focus complex.
Murashima
Y L
YL
Department of Neurophysiology, Tokyo Institute of Psychiatry, Japan. murasima@prit.go.jp
Yoshii
M
M
Suzuki
J
J
D000818:Animals; D003124:Colorimetry; D004195:Disease Models, Animal; D004829:Epilepsy, Generalized / Q000201:enzymology / Q000503:physiopathology*; D005110:Extracellular Space / Q000737:chemistry / Q000201:enzymology; D006624:Hippocampus / Q000737:chemistry / Q000201:enzymology / Q000503:physiopathology*; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008818:Mice, Neurologic Mutants; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D010296:Parietal Lobe / Q000737:chemistry / Q000201:enzymology / Q000503:physiopathology*; D013702:Temporal Lobe / Q000737:chemistry / Q000201:enzymology / Q000503:physiopathology*
D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse