Нейронные механизмы пространственной ориентации в норме и при болезни Альцгеймера
DOI:
https://doi.org/10.33910/2687-1270-2026-7-2-176-194Ключевые слова:
болезнь Альцгеймера, блуждающее поведение, нейронные сети, восприятие ориентиров, синаптическая пластичность, дофамин, аденозинАннотация
Необходимость поиска методов ослабления различных симптомов болезни Альцгеймера вызвана ее большой распространенностью, а сложная патофизиология требует комбинированных методов лечения. В настоящей работе проведен анализ возможного механизма ухудшения пространственной ориентации при болезни Альцгеймера. В основе этого механизма лежит нарушение восприятия сенсорных стимулов, служащих ориентирами, и перекартирования клеток места. Эти нарушения являются следствием изменений функционирования топографически организованных взаимосвязанных нейронных цепей: гиппокамп — базальные ганглии — ядро реуниенс — гиппокамп, кора — базальные ганглии — таламус — кора и кора — базальные ганглии — клауструм — кора, которые включают ретросплениальную, первичные и высшие области коры. С учетом данных о дефиците дофамина и повышенной экспрессии аденозиновых А2А‑рецепторов при болезни Альцгеймера проведен анализ влияний дофамина и аденозина на функционирование указанных цепей. Из него следует, что антагонисты А2А‑рецепторов в сочетании с низкими дозами дофаминергических препаратов, способствуя ослаблению ингибирования таламических ядер и клауструма со стороны базальных ганглиев, могут улучшить восприятие ориентиров клетками места в коре, гиппокампе, клауструме и стриатуме, не вызывая значительных побочных эффектов. Эти препараты могут использоваться в сочетании с низкими дозами современных аллостерических модуляторов мускариновых М1‑рецепторов для компенсации дефицита ацетилхолина. Предлагаемый механизм является унифицированным и может быть применим к восприятию разномодальных сенсорных стимулов, зрительных, звуковых или обонятельных. В пользу следствий предлагаемого механизма свидетельствуют данные, полученные в клинических испытаниях и в экспериментальных моделях болезни Альцгеймера на грызунах.
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