Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65166710.31857/S0869813924030108CPFZPMEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleAnalysis of the State of Glutamate- and Gaba-Ergic Neurons in the Inferior Colliculi of Krushinsky – Molodkina Strain Rats at Early Stages of EpileptogenesisАнализ состояния глутамат- и гамкергических нейронов нижних бугров четверохолмия крыс линии Крушинского – Молодкиной на ранних этапах эпилептогенезаNikolaevaS. D.НиколаеваС. Д.
Russian Federation
sveta.nikolaeva@gmail.comNikitinaL. S.НикитинаЛ. С.
Russian Federation
sveta.nikolaeva@gmail.comGlazovaM. V.ГлазоваМ. В.
Russian Federation
sveta.nikolaeva@gmail.comBakhteevaV. T.БахтееваВ. Т.
Russian Federation
sveta.nikolaeva@gmail.comChernigovskayaE. V.ЧерниговскаяЕ. В.
Russian Federation
sveta.nikolaeva@gmail.comInstitute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesИнститут эволюционной физиологии и биохимии им. И.М. Сеченова РАН15032024110348049801022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/651667

Disturbances in the neurotransmitter systems during the development of temporal lobe epilepsy have been most detailed studied in forebrain structures – in the temporal cortex, amygdala, and hippocampus [1, 2]. It is known that during the formation of temporal lobe epilepsy in the model of audiogenic kindling there is a spread of epileptiform activity from brainstem to forebrain structures. However, the molecular mechanisms of neurotransmission dysregulation in the inferior colliculi in rodents with genetic prone to audiogenic seizures during epileptogenesis remain unknown. Changes in neurotransmitter systems of inferior colliculi may contribute significantly to the recruitment of forebrain structures during the initial stages of epileptogenesis.

The current work provides a comprehensive analysis of activity markers of glutamate- and GABA-ergic neurons in inferior colliculi of Krushinsky – Molodkina (KM) rats genetically prone to audiogenic seizures. A modified audiogenic kindling protocol was used to model the early stages of temporal lobe epilepsy development. In this protocol rats were subjected to daily audiogenic seizures for seven days. Naive KM rats were used as controls.

Although the rodent’s predisposition to audiogenic seizures is often associated with disruptions in GABAergic transmission, no significant changes were found in the expression of GABA synthesis enzymes or the α1 subunit of the GABAA receptor in the brains of KM rats, either 24 hours or a week after their last convulsive seizure. However, 24 hours after the last audiogenic seizure, an increase in glutamatergic transmission in the inferior colliculi was observed: the activity of ERK 1/2 kinases and the exocytosis protein synapsin 1 increased, as well as the expression of VGLUT1 and VGLUT2 and the synaptic protein SV2B. One week after the last seizure, only an increase in VGLUT1 content in the inferior colliculi was observed, suggesting that persistent changes occur in the neurons of forebrain structures, in particular, the temporal cortex.

Нарушения в работе нейромедиаторных систем при моделировании развития височной эпилепсии наиболее детально изучены в структурах переднего мозга – в височной коре, амигдале и гиппокампе. Известно, что в ходе формирования височной эпилепсии в модели аудиогенного киндлинга наблюдается распространение эпилептиформной активности из стволовых отделов в вышележащие отделы мозга. Однако молекулярные механизмы нарушения регуляции нейротрансмиссии в нижних буграх четверохолмия у грызунов с генетической предрасположенностью к аудиогенным судорожным припадкам в ходе эпилептогенеза остаются неизученными. Изменения в работе нейромедиаторных систем нижних бугров четверохолмия на начальных этапах эпилептогенеза может вносить существенный вклад в эпилептизацию структур переднего мозга. В настоящей работе проведен комплексный анализ маркеров активности глутамат- и ГАМКергических нейронов в нижних буграх четверохолмия крыс Крушинского – Молодкиной (КМ), генетически предрасположенных к аудиогенным судорожным припадкам. Для моделирования ранних этапов развития височной парциальной эпилепсии был использован модифицированный протокол аудиогенного киндлинга, в ходе которого крыс подвергали ежедневным аудиогенным судорожным припадкам в течение семи дней. В качестве контроля использовали наивных крыс КМ. Несмотря на то, что предрасположенность к аудиогенным судорожным припадкам у грызунов часто связывают с нарушениями в ГАМКергической передаче сигнала, нам не удалось выявить значимых изменений в экспрессии ферментов синтеза ГАМК и субъединицы α1 GABAA-рецептора у крыс линии КМ ни через сутки, ни через неделю после завершения последнего судорожного припадка. При этом через сутки после завершения эксперимента наблюдалось усиление глутаматергической трансмиссии в нижних буграх четверохолмия: повышался уровень активности ERK1/2-киназ и белка экзоцитоза синапсина 1, а также экспрессия VGLUT1 и VGLUT2 и синаптического белка SV2B. Через неделю после последнего припадка наблюдалось только повышенное содержание VGLUT1 в нижних буграх четверохолмия, это свидетельствует о том, что устойчивые изменения затрагивают нейроны вышележащих структур, в частности, височной коры.

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