ИММУНОЛОГИЧЕСКИЕ НАРУШЕНИЯ И КОГНИТИВНЫЙ ДЕФИЦИТ ПРИ СТРЕССЕ И ФИЗИОЛОГИЧЕСКОМ СТАРЕНИИ. ЧАСТЬ I: ПАТОГЕНЕЗ И ФАКТОРЫ РИСКА

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Аннотация

В обзоре рассматриваются иммунологические механизмы развития когнитивного дефицита при стрессе и физиологическом старении,
а также предлагаются новые подходы к терапии подобных состояний. У млекопитающих сложный комплекс адаптационных механизмов представлен в виде триады, образованной центральной нервной, иммунной и эндокринной системой, которые постоянно обмениваются сигналами в виде нервных импульсов и растворимых медиаторов. Головной мозг, защищенный гематоэнцефалическим барьером (ГЭБ) от проникновения потенциально опасных клеток и растворимых факторов, самостоятельно продуцирует цитокины, которые вместе с другими нейромедиаторами регулируют процессы обучения и формирования памяти, а также нейрогенез у взрослых особей. Стресс любого происхождения сопровождается ростом концентрации цитокинов в крови и повышением проницаемости ГЭБ. В результате циркулирующие в крови цитокины могут проникать в мозг, где начинают выполнять «неиммунологические» функции. Ослабление барьерной функции ГЭБ и развивающаяся нейровоспалительная реакция способствуют массовой миграции дендритных клеток и лимфоцитов из периваскулярного пространства в паренхиму мозга. Вторжение чуждых центральной нервной системе медиаторов и иммунных клеток вызывает развитие когнитивных расстройств как у человека, так и у экспериментальных животных. Повторные эпизоды стресса способствуют накоплению в головном мозге иммунных клеток, обусловливают необратимое изменение проницаемости ГЭБ, нарушают нейрогенез у взрослых особей в зубчатой извилине гиппокампа. Подобные неблагоприятные изменения протекают в головном мозге пожилых людей при нормальном физиологическом старении. Более того, длительном стрессе и при физиологическом старении возникают сходные иммунологические и гормональные нарушения, прежде всего гиперактивация и последующее истощение гипоталамо-гипофизарно-надпочечниковой оси, накопление избыточного количества регуляторных Т клеток, снижение продукции дегидроэпиандростерона.

Об авторах

А. Л. Пухальский

Медико-генетический научный центр, Москва, Российская Федерация

Email: osugariver@yahoo.com

PhD, professor, chief research scientist of the Department of Cystic Fibrosis of Research Centre of Medical Genetics (RCMG). Address: 1, Moskvorech’e Street, Moscow, RF, 115478.

Россия

Г. В. Шмарина

Медико-генетический научный центр, Москва

Автор, ответственный за переписку.
Email: osugariver@yahoo.com
кандидат медицинских наук, ведущий научный сотрудник отдела муковисцидоза МГНЦ Россия

В. А. Алёшкин

Московский НИИ эпидемиологии и микробиологии им. Г.Н. Габричевского

Email: info@gabrich.com
доктор биологических наук, профессор, директор МНИИЭМ им. Г.Н. Габричевского Россия

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