Гипотеза взаимосвязи эпигенетических факторов с транспозонами в формировании памяти

В обзорной статье описана гипотеза, согласно которой драйверами эпигенетической регуляции в формировании памяти являются мобильные генетические элементы, влияющие на экспрессию специфических генов в головном мозге. В подтверждение приведены результаты научных исследований о закономерной активации транспозонов в нейрональных стволовых клетках при дифференцировке нейронов. Данные процессы происходят в зоне нейрогенеза – зубчатой извилине гиппокампа, где определяются наибольшая активность мобильных генетических элементов и их инсерции в локусы вблизи генов, экспрессируемых нейронами с их активацией. В экспериментах по изменению активности ацетилтрансферазы гистонов, ингибированию ДНК-метилтрансферазы и обратной транскриптазы было показано вовлечение эпигенетических факторов и ретроэлементов в механизмы формирования памяти. В то же время в ряде работ на разных животных продемонстрировано сохранение долговременной памяти без участия синаптической пластичности. Полученные данные позволяют предположить, что транспозоны, являющиеся высокочувствительными сенсорами генома к различным средовым и внутренним воздействиям, формируют память на уровне ядерного кодирования. Это отражается в изменении синаптической пластичности, чем можно объяснить сохранение долговременной памяти после устранения синаптических связей у животных. Подтверждением служат факты происхождения от мобильных генетических элементов белков, непосредственно участвующих в формировании памяти, в том числе в передаче генетической информации через синапсы между нейронами (белок Arc). Транспозоны – источники длинных некодирующих РНК и микроРНК, роль которых в консолидации памяти описана. Патологическая активация мобильных генетических элементов является вероятной причиной нейродегенеративных болезней с нарушением памяти. Анализ научной литературы позволил нам обнаружить данные об изменениях экспрессии 40 микроРНК, произошедших от транспозонов, при болезни Альцгеймера. Для 24 из этих микроРНК описаны механизмы регуляции генов, участвующих в функционировании головного мозга. Сделано предположение, что установленные нами микроРНК могли бы стать потенциальными инструментами для регуляции активности транспозонов в головном мозге с целью улучшения памяти.

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