-Original-

The Roles of Dominance of the Nitric Oxide Fractions Nitrate and Nitrite in the Epilepsy-Prone EL Mouse Brain

Yasuhiko Kawakami^1,2, Yoshiya L. Murashima³, Mitsutoshi Tsukimoto⁴, Hajime Okada¹, Chiharu Miyatake¹, Atsushi Takagi¹, Juri Ogawa¹ and Yasuhiko Itoh¹

¹Department of Pediatrics, Nippon Medical School, Tokyo, Japan
²Department of Pediatrics, Nippon Medical School Musashi Kosugi Hospital, Kanagawa, Japan
³Graduate School of Human Health Science, Tokyo Metropolitan University, Tokyo, Japan
⁴Department of Radiation Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

Background: Oxidative stress is thought to be closely related to epileptogenesis. We have previously reported that nitric oxide (NO) levels are higher in epilepsy-prone EL mice between the ages of 3 and 8 weeks than in control mice. However, NO is divided into two fractions, nitrite (NO₂) and nitrate (NO₃), which appear to play different roles in epileptogenesis.
Methods: NO₂ and NO₃ levels were measured, in EL mice and the control mice, in the parietal cortex, which is thought to be the primary epileptogenetic center in EL mice, and measured in the hippocampus, which is thought to be the secondary center.
Results: NO₃ levels in the hippocampus and parietal cortex of the immature EL mice (3 to 8 weeks of age) were significantly higher than those in the control mice; NO₂ levels were significantly higher in the EL mice throughout the study period. The NO₃ levels were significantly higher than the NO₂ levels in the immature EL mice, but after the onset of ictogenesis at 10 weeks of age, the relative levels of the two fractions reversed.
Conclusion: The reversal of the NO fraction distribution at the onset of seizures that we observed may be related to the developmental process of seizure susceptibility in the neural network of EL mice.

J Nippon Med Sch 2021; 88: 189-193

Keywords
nitric oxide (NO), nitrite (NO₂), nitrate (NO₃), EL mice, seizure susceptibility

Correspondence to
Yasuhiko Kawakami, Department of Pediatrics, Nippon Medical School Musashi Kosugi Hospital, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan
kawakami@nms.ac.jp

Received, August 20, 2019
Accepted, May 25, 2020