Влияние кардарина на экспрессию генов белков, вовлеченных в эпилептогенез, в гиппокампе крыс в литий-пилокарпиновой модели височной эпилепсии
- Авторы: Харисова А.Р.1, Рогинская А.И.1, Зубарева О.Е.1
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Учреждения:
- Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН
- Выпуск: Том 110, № 5 (2024)
- Страницы: 814-836
- Раздел: ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ
- URL: https://cardiosomatics.ru/0869-8139/article/view/651647
- DOI: https://doi.org/10.31857/S0869813924050115
- EDN: https://elibrary.ru/BKJEXJ
- ID: 651647
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Аннотация
В последние годы активно обсуждается роль в патогенезе эпилепсии астро- и микроглиальных клеток и связанного с ними нейровоспаления. Эти клетки могут быть в разных функциональных состояниях, крайние из которых A1 и M1 фенотипы продуцируют преимущественно провоспалительные (способствующие эпилептогенезу) белки, а A2 и M2 фенотипы – противовоспалительные (предотвращающие эпилептогенез) белки. Предполагается, что использование препаратов, способных стимулировать поляризацию от М1 и А1 к М2 и А2 фенотипам, может стать успешной стратегией лечения эпилепсии. К таким препаратам относятся агонисты ядерных рецепторов, активируемых пролифератором пероксисом (PPARs). Целью данной работы стало изучение изменений экспрессии микро- и астроглиальных белков, вовлеченных в регуляцию эпилептогенеза, в дорзальном гиппокампе крыс в литий-пилокарпиновой модели височной эпилепсии и исследование влияния на эти процессы агониста PPAR бета/дельта кардарина. Кардарин вводили на начальных этапах эпилептогенеза (в течение 7 дней после индукции TLE модели), через два месяца (хроническая фаза модели) проводили анализ экспрессии генов интереса в дорзальном гиппокампе методом ОТ-ПЦР в реальном времени. Проведенное исследование выявило изменение экспрессии генов астро- и микроглиальных белков в процессе эпилептогенеза, в основном связанное с усилением нейровоспалительных процессов и ослаблением нейропротекторных свойств этих клеток. У TLE крыс увеличивалась экспрессия генов маркеров активации астро- (Gfap) и микроглии (Aif1), про- (Il1b, Nlrp3) и противовоспалительных (Il1rn) белков, маркеров фенотипа A1 астроцитов (Lcn2, Gbp2) и ростовых факторов (Bdnf, Fgf2). Экспрессия гена защитного М2 фенотипа Arg1 снижалась у TLE крыс. Наиболее яркий эффект введения кардарина проявился в усилении экспрессии гена маркера A2 фенотипа астроцитов S100a10.
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Об авторах
А. Р. Харисова
Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН
Email: ZubarevaOE@mail.ru
Россия, Санкт-Петербург
А. И. Рогинская
Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН
Email: ZubarevaOE@mail.ru
Россия, Санкт-Петербург
О. Е. Зубарева
Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН
Автор, ответственный за переписку.
Email: ZubarevaOE@mail.ru
Россия, Санкт-Петербург
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