Involvement of Glutamine Synthetase in the Development of Hyperbaric Oxygen Seizures

• Published in: Journal of evolutionary biochemistry and physiology Vol. 58; no. 1; pp. 158 - 166
• Main Authors: Alekseeva, O. S., Zhilyaev, S. Yu, Platonova, T. F., Tsyba, D. L., Kirik, O. V., Korzhevskii, D. E., Demchenko, I. T.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2022; Springer Nature B.V
• Subjects: Animal Physiology; Biochemistry; Biomedical and Life Sciences; Central nervous system; EEG; Enzymatic activity; Epilepsy; Evolutionary Biology; Experimental Papers; Glutamate-ammonia ligase; Glutamatergic transmission; Glutamine; Hyperbaric oxygen; Hyperoxia; Latency; Life Sciences; Methionine; Neurotransmission; Seizures; methionine sulfoximine; hyperbaric oxygen; glutamine synthetase; convulsions; glutamatergic system
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093022010148

Hyperbaric oxygen (HBO
2
) causes a toxic effect on the central nervous system via poorly understood mechanisms. The aim of this study was to test the hypothesis that HBO
2
inhibits the activity of glutamine synthetase (GS) in the brain and increases the level of glutamatergic neurotransmission, thus leading to the development of epileptiform activity in the EEG and tonic-clonic motor seizures. In experiments on awake rats exposed to oxygen partial pressure of 4.65 ATA, the seizure onset latency was determined in animals with intact and inhibited GS. The enzymatic activity of GS was irreversibly suppressed using the selective inhibitor L-methionine sulfoximine (MSO). It was found that the development of seizures under hyperbaric hyperoxia correlated with a decrease in the GS level in the brain. MSO accelerated the development of oxygen-induced seizures. The obtained data indicate that the manifestation of convulsive syndrome under extreme hyperoxia depends on the enzymatic activity of GS, a key enzyme regulating glutamatergic neurotransmission.