CHRONIC DYSREGULATION OF GLUTAMATERGIC TRANSMISSION IN THE HIPPOCAMPUS OF KRUSHINSKY–MOLODKINA RATS INDUCED BY REPEATED EPILEPTIFORM SEIZURES

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Temporal lobe epilepsy is characterised by the development of associated neurological and psychiatric disorders. One of the possible causes is obviously a disturbance in the balance of the excitatory and inhibitory neurotransmitter systems of the hippocampus. Chronic abnormalities in the molecular mechanisms of regulation of hippocampal glutamatergic system activity in temporal lobe epilepsy are currently poorly understood. In the present study, we used Krushinsky–Molodkina (KM) rats subjected to repeated audiogenic seizures to simulate temporal lobe epilepsy. Molecular mechanisms of regulation of glutamate production by hippocampal neurons were analysed one week after the end of short-term (14 seizures) and long-term (21 seizures) kindling. In the hippocampus of КM rats, kindling results in activation of ERK1/2 kinases as well as activation of the transcription factor CREB and increased expression of the transcription factor Fra1, glutaminase and the vesicular glutamate transporters VGLUT1 and 2, that is proteins responsible for glutamate production. These data indicate increased activity of glutamatergic hippocampal neurons persisting for a week at rest after the completion of the last audiogenic stimulation. Enhanced expression of mGluR1 glutamate receptors, whose activation is known to result in Ca2+ release and increased excitotoxicity, is also shown. Long-term enhancement of glutamatergic transmission induced by repeated epileptiform seizures is not only responsible for further epileptogenesis, but may also underlie the development of neurodegenerative complications.

作者简介

E. Aleksandrova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: chern755@mail.ru
Russia, St. Petersburg

A. Ivlev

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: chern755@mail.ru
Russia, St. Petersburg

A. Kulikov

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: chern755@mail.ru
Russia, St. Petersburg

L. Nikitina

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: chern755@mail.ru
Russia, St. Petersburg

M. Glazova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: chern755@mail.ru
Russia, St. Petersburg

E. Chernigovskaya

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

编辑信件的主要联系方式.
Email: chern755@mail.ru
Russia, St. Petersburg

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版权所有 © Е.П. Александрова, А.П. Ивлев, А.А. Куликов, Л.С. Никитина, М.В. Глазова, Е.В. Черниговская, 2023

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