Трансляционные модели на животных в исследовании регуляции стрессового ответа и сложных механизмов действия глюкокортикоидов: ПАТОФИЗИОЛОГИЯ — МЕДИЦИНЕ

Сарнг Саналович  Пюрвеев; Алеся Сергеевна  Оськина; София Владимировна  Уланова

doi:10.56871/RBR.2025.83.69.004

Трансляционные модели на животных в исследовании регуляции стрессового ответа и сложных механизмов действия глюкокортикоидов

ПАТОФИЗИОЛОГИЯ — МЕДИЦИНЕ

Сарнг Саналович Пюрвеев Санкт-Петербургский государственный педиатрический медицинский университет; Институт экспериментальной медицины https://orcid.org/0000-0002-4467-2269
Алеся Сергеевна Оськина Санкт-Петербургский государственный педиатрический медицинский университет https://orcid.org/0009-0000-8164-2504
София Владимировна Уланова Санкт-Петербургский государственный педиатрический медицинский университет https://orcid.org/0009-0004-3809-058X

Ключевые слова:

hypothalamic-pituitary-adrenal axis translational models zebrafish burrowing rodents stress glucocorticoids гипоталамо-гипофизарно-надпочечниковая ось трансляционные модели Данио-рерио норные грызуны стресс глюкокортикоиды

Аннотация

На основании анализа литературы в данном обзоре авторы систематизировали сведения о реакции организма на стресс, основных структурах, участвующих в этом процессе, их поэтапном формировании, развитии и взаимосвязях, обеспечивающих регуляцию ответа на стрессовое воздействие. Отдельно раскрыта роль применения трансляционных моделей животных в изучении развития гипоталамо-гипофизарно-надпочечниковой оси, преимущества и возможные ограничения, которые необходимо учитывать при планировании исследования для выбора подходящей модели. Гипоталамо-гипофизарно-надпочечниковая ось — сложная нейроэндокринная система, участвующая в реализации ответа на воздействие стрессора посредством многоуровневых взаимодействий. Организму необходимо пройти через несколько критических периодов развития, чтобы обеспечить правильное функционирование гипоталамо-гипофизарно-надпочечниковой оси и соответствующие поведенческие и физиологические реакции на стресс во взрослом возрасте. Активность гипоталамо-гипофизарно-надпочечниковой оси колеблется в течение суток, эти изменения обеспечиваются водителем циркадного ритма и супрахиазматическим ядром, регулирующим суточные ритмы выработкиглюкокортикоидов. Гетеродимерные геныCLOCK/BMAL1в совокупности с другими транскрипционными факторами отвечают за циркадные колебания экспрессии генов под контролем системы биологических часов. Ультрадианное изменение секреции зависит от пульсирующего высвобождения кортикостерона и адренокортикотропного гормона в ответ на различное время действия стимула и сигналов обратной связи в пределах гипоталамо-гипофизарно-надпочечниковой оси. Глюкокортикоиды воздействуют на клетки посредством геномных и негеномных механизмов. Негеномный путь обеспечивается взаимодействием с ассоциированными с плазматической мембраной изоформами глюкокортикоидного и минералкортикоидного рецепторов. Наличие этих изоформ подтверждается в лимбической системе, гиппокампе, дендритных шипиках, пре- и постсинаптических мембранах. В качестве наиболее доступных и часто используемых моделей для изучения стрессового ответа подробно рассмотрены следующие модели: рыбы Данио-рерио, крысы и мыши. В данной статье впервые проведен сравнительный анализ рыб Данио-рерио, крыс и мышей с точки зрения трансляционной нейробиологии, рассмотрены аспекты формирования их гипоталамо-гипофизарно-надпочечниковой оси (строение глюкокортикоидного рецептора, течение стресс-гипореактивного периода, особенности основной стрессовой сигнальной молекулы), доступность, специфичность и другие характеристики, которые необходимо учитывать при выборе экспериментальной модели.

Биографии авторов

Сарнг Саналович Пюрвеев, Санкт-Петербургский государственный педиатрический медицинский университет; Институт экспериментальной медицины

к.м.н., доцент кафедры патологической физиологии с курсом иммунопатологии

Алеся Сергеевна Оськина, Санкт-Петербургский государственный педиатрический медицинский университет

студентка 5-го курса, педиатрический факультет

София Владимировна Уланова, Санкт-Петербургский государственный педиатрический медицинский университет

студентка 5-го курса, педиатрический факультет

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