КЛЕТОЧНАЯ ТЕРАПИЯ КАК СПОСОБ КОРРЕКЦИИ НАРУШЕНИЙ НЕЙРОГЕНЕЗА ВО ВЗРОСЛОМ МОЗГЕ В МОДЕЛИ БОЛЕЗНИ АЛЬЦГЕЙМЕРА
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Ключевые слова

болезнь Альцгеймера
нейрогенез
мезенхимальные стволовые клетки
трансгенные самки линии 5XFAD

Как цитировать

Чаплыгина, А. В., Жданова, Д. Ю., Ковалев, В. И., Полтавцева, Р. А., Медвинская, Н. И., & Бобкова, Н. В. (2021). КЛЕТОЧНАЯ ТЕРАПИЯ КАК СПОСОБ КОРРЕКЦИИ НАРУШЕНИЙ НЕЙРОГЕНЕЗА ВО ВЗРОСЛОМ МОЗГЕ В МОДЕЛИ БОЛЕЗНИ АЛЬЦГЕЙМЕРА. Российский физиологический журнал им. И. М. Сеченова, 108(1), 59–84. https://doi.org/10.31857/S0869813922010046

Аннотация

В основу настоящей работы положена гипотеза о нарушении нейрогенеза в мозге при болезни Альцгеймера (БА), приводящем к некомпенсированной гибели нейронов и ухудшению памяти. Предполагается, что лечение может быть осуществлено путем активации эндогенного нейрогенеза при помощи клеточной терапии. В нашем исследовании для внутримозговой трансплантации использовали мезенхимальные стволовые клетки (МСК), выделенные из Вартонова студня пупочного канатика человека, имеющие ряд существенных преимуществ по сравнению с МСК, выделенными из других тканей. Эксперименты выполнены на трансгенных (Tg) 8- 9-месячных самках мышей линии 5XFAD – модели наследственной формы БА. Для оценки эффектов трансплантации МСК во фронтальную кору головного мозга анализировались состояние пространственной памяти в сопоставлении с морфофункциональными характеристиками ниш взрослого нейрогенеза – субгранулярной зоны зубчатой фасции гиппокампа (SGZ) и субвентрикулярной зоны боковых желудочков головного мозга (SVZ), височной зоны неокортекса и СА1/СА3 полей гиппокампа – структур, ответственных за обучение и память. Анализировали иммунопозитивность к BrdU и к маркерам нейрональной дифференцировки: нестину, даблкортину, 3-бета-тубулину, NeuN, МАР2 и GFAP. Tg мыши характеризовались нарушением соотношения интенсивности пролиферативной активности в SGZ/SVZ и снижением нейрональной плотности в коре головного мозга и гиппокампе. Позитивный эффект МСК на память мышей проявился через два месяца после трансплантации. На этом же сроке МСК были обнаружены только в мозге Tg животных. Под влиянием МСК у Tg и nTg мышей возрастала плотность BrdU+ позитивных клеток в нишах взрослого нейрогенеза, однако только в гиппокампе Tg мышей отмечалось снижение числа амилоидных бляшек, повышение плотности нейронов и иммунопозитивности к синаптофизину, а также снижение числа клеток с апоптозом. Позитивное действие МСК у Tg животных проявилось в гиппокампе – структуре, отдаленной от места трансплантации клеток во фронтальной коре, что свидетельствует о паракринном действии МСК, валидности химерной модели и перспективах клинического использования МСК для лечения БА.

https://doi.org/10.31857/S0869813922010046
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