Эпидемиологические исследования показывают, что во всём мире, в том числе в РФ, наблюдается устойчивый рост числа пациентов с когнитивными нарушениями, связанными с нейродегенеративными заболеваниями и различными аффективными расстройствами. В связи с этим существует запрос на разработку более действенных терапевтических подходов к их коррекции. Установлено, что регулярная физическая нагрузка способствует улучшению когнитивных функций и подавляет симптомы депрессии. Работающие мышцы секретируют биологически активные вещества — миокины, регулирующие восстановление самих мышц, а также регулирующие функции внутренних органов, желёз внутренней секреции, иммунной системы и мозга. Результатом является скоординированный ответ органов и систем, направленный на восстановление функциональной активности организма после физической нагрузки. В частности, улучшается память и способность к обучению. Пациенты с когнитивными нарушениями или депрессией часто не способны вовлечься в регулярную физическую активность из-за физических ограничений или ослабления мотивации. В связи с этим фармацевтические препараты, имитирующие эффекты мышечной активности, являются перспективной терапевтической опцией. Одним из направлений может стать создание препаратов на основе миокина иризина, который вырабатывается во время физической нагрузки и оказывает целый ряд благотворных эффектов на когнитивные функции и настроение. В этом обзоре представлены данные по влиянию физической нагрузки на когнитивные функции в норме и при патологии, описано физиологическое действие иризина, представлены предполагаемые механизмы действия иризина на когнитивные функции и симптомы депрессии.
Предпросмотр статьи
Идентификаторы и классификаторы
- SCI
- Биология
Деменция и депрессия входят в число важнейших проблем гериатрии. Деменция характеризуется приобретёнными когнитивными нарушениями, приводящими к заметному ухудшению способности пациента к обучению, работе, общению и, в конце концов, к нарушению способности поддерживать нормальный образ жизни [1]. По этиологии и патогенезу можно выделить две категории деменций: 1) наблюдающиеся при нейродегенеративных заболеваниях — болезни Альцгеймера, деменции с тельцами Леви, болезни Паркинсона и лобно-височной долевой дегенерации; 2) возникающие при иных, не нейродегенеративных патологиях, таких как гидроцефалия, черепно-мозговая травма, инфекции, иммунные нарушения, опухоли, отравления и метаболические заболевания [1]. В 2017 году глобальная оценка численности пациентов с диагнозом деменция составляла приблизительно 50 миллионов человек, и ожидалось, что каждые 20 лет их численность будет удваиваться [2]. Поддержание когнитивных функций у стареющего населения является важной задачей, поскольку деменция напрямую влияет на качество жизни пожилых людей и создаёт значительную нагрузку на общество, семьи и систему здравоохранения. Депрессия является ещё более распространённым серьёзным ментальным заболеванием, которое касается почти 300 миллионов людей по всему миру [3] и также является одной из главных причин временной нетрудоспособности с невыходом на работу [4].
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Ионы меди (Cu2+) в концентрации 25–50 мкМ стимулируют вызванную липополисахаридом (ЛПС) продукцию оксида азота (NO) в культурах глиальных клеток, полученных из коры головного мозга крыс и содержащих как астроциты, так и клетки микроглии. Более высокая концентрация Cu2+ (100 мкМ) при стимуляции ЛПС не вызывала достоверного повышения NO в среде инкубации, а при 200 мкМ Cu2+ происходило снижение этого параметра по сравнению с ЛПС. Ионы Cu2+ в этих концентрациях снижали жизнеспособность культивируемых клеток. Видимо, снижение жизнеспособности клеток не связано с накоплением нитритов, так как добавление в среду культивирования даже 100 мкМ нитрита натрия не снижало выживаемость клеток и не влияло на цитотоксичность Cu2+. Исследование клеток микроглии (маркер IBA1) показало, что в культурах, обработанных ЛПС, микроглия имела преимущественно распластанную амебоидную морфологию, характерную для активированной микроглии. Кроме того, под действием ЛПС происходило увеличение площади профильного поля тела клеток и периметра. В концентрации 25 мкМ ионы Cu2+ не влияли на морфологические изменения клеток микроглии, связанные с воспалительным фенотипом. Нельзя исключать, что усиление ионами меди продукции NO, вызванной ЛПС, опосредовано астроцитами.
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- Издательство
- ИБМХ
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- Россия, Москва
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- Пономаренко Елена Александровна (Директор)
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