Аннотация
Для височной эпилепсии характерно развитие сопутствующих неврологических нарушений и психических заболеваний. Одной из возможных причин их возникновения, очевидно, являются нарушения в балансе возбуждающих и тормозных нейротрасмиттерных систем гиппокампа. Хронические нарушения в молекулярных механизмах регуляции активности глутаматергической системы гиппокампа при височной эпилепсии в настоящее время малоизучены. В настоящей работе мы использовали крыс линии Крушинского-Молодкиной (КМ), подвергнутых многократным аудиогенным судорожным припадкам, для моделирования височной эпилепсии. Анализ молекулярных механизмов регуляции продукции глутамата нейронами гиппокампа был проведен через неделю после окончания стандартного (14 судорожных припадка) и длительного (21 судорожных припадка) киндлинга. В гиппокампе крыс КМ в результате киндлинга происходит активация ERK1/2-киназ, а также активация транскрипционного фактора CREB, усиление экспрессии глутаминазы и везикулярных транспортеров глутамата VGLUT1 и 2 и транскрипционного фактора Fra1, то есть белков, отвечающих за продукцию глутамата. Эти данные свидетельствует о повышении активности глутаматергических нейронов гиппокампа, сохраняющейся в течение недели после завершения последней аудиогенной стимуляции. Также показано усиление экспрессии mGluR1-рецепторов глутамата, активация которых приводит к высвобождению Ca2+ и может вызывать эксайтотоксичность. Долговременное усиление глутаматергической трансмиссии, вызванное многократными эпилептиформными припадками, является причиной не только дальнейшего эпилептогенеза, но и может лежать в основе развития нейродегенерации.
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