БИОХИМИЯ, 2019, том 84, вып. 11, с. 1622–1648

УДК 57.052;57.053;57.054

Биохимические механизмы и трансляционное значение чувствительности гиппокампа к дистантному фокальному повреждению мозга: цена стрессорного ответа

Обзор

© 2019 Н.В. Гуляева 1,2 *

Институт высшей нервной деятельности и нейрофизиологии РАН, 117485 Москва, Россия; электронная почта: nata_gul@mail.ru

Научно-практический психоневрологический центр им. З.П. Соловьева ДЗМ, 115419 Москва, Россия

Поступила в редакцию 07.06.2019
После доработки 24.08.2019
Принята к публикации 24.08.2019

DOI: 10.1134/S0320972519110083

КЛЮЧЕВЫЕ СЛОВА: гиппокампа, стресс, гипоталамо-гипофизарно-надпочечниковая ось, кортикостероиды, глюкокортикоидный рецептор, минералокортикоидный рецептор, цитокины, инсульт, черепномозговая травма, депрессия, деменция.

Аннотация

Фокальные поражения мозга (в первую очередь инсульт и черепномозговая травма) с большой вероятностью индуцируют развитие впоследствии когнитивных и депрессивных расстройств, часто коморбидных. Ассоциация этих осложнений с изменениями гиппокампа (несмотря на отсутствие первичного повреждения этой структуры), а также отсутствие четкой зависимости между вероятностью развития депрессии и деменции и тяжестью и локализацией первичного поражения послужили основой для новой гипотезы о дистантном повреждении гиппокампа, как ключевом звене патогенеза когнитивных и психических расстройств. В соответствии с этой гипотезой избыток кортикостероидов, секретированных после фокального поражения мозга, особенно у пациентов с аномальным стрессорным ответом в связи с дисфункцией гипоталамо-гипофизарно-надпочечниковой оси (ГГНО), взаимодействует с кортикостероидными рецепторами гиппокампа, индуцируя сигнальные пути, стимулирующие нейровоспаление и последующие события, включая нарушения нейрогенеза и нейродегенерацию. В этой статье проанализированы молекулярные и клеточные механизмы, ассоциированные с регуляторной ролью ГГНО и множественными функциями кортикостероидных рецепторов гиппокампа. Функциональные и структурные повреждения гиппокампа, региона мозга, селективно уязвимого при действии внешних факторов и отвечающего на них повышением секреции цитокинов, составляют основу для нарушения когнитивных функций и развития психопатологии. Эта концепция подтверждается собственными экспериментальными данными, результатами других групп, а также результатами проспективных клинических исследований постинсультных осложнений. Предложены клинически релевантные биохимические подходы к прогнозу риска постинсультных/посттравматических когнитивных и депрессивных расстройств путем оценки биохимических маркеров индивидуального стрессорного ответа пациента. Обсуждены патогенетически обоснованные пути предупреждения последствий фокального поражения мозга воздействием на ключевые молекулярные мишени, ассоциированные с дисфункцией гиппокампа.

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* Автор является выпускником кафедры биохимии биологического факультета МГУ им. М.В. Ломоносова.

Финансирование

Работа поддержана Российским фондом фундаментальных исследований (грант № 18-00-00125) (стресс, депрессия) и Программой президиума Российской академии наук «Фундаментальные основы технологии физиологических адаптаций (дистантное повреждение гиппокампа)».

Конфликт интересов

Автор заявляет об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит каких-либо исследований с участием людей или использованием животных в качестве объектов исследований.

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