Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC40510.15690/vramn.v69i7-8.1107PHYSIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ФИЗИОЛОГИИIMMUNE DYSFUNCTION AND COGNITIVE DEFICIT IN STRESS AND PHYSIOLOGICAL AGING. PART II: NEW APPROACHES TO COGNITIVE DISORDER PREVENTION AND TREATMENTИММУНОЛОГИЧЕСКИЕ НАРУШЕНИЯ И КОГНИТИВНЫЙ ДЕФИЦИТ ПРИ СТРЕССЕ И ФИЗИОЛОГИЧЕСКОМ СТРОЕНИИ. ЧАСТЬ II: НОВЫЕ ПОДХОДЫ К ПРОФИЛАКТИКЕ И ЛЕЧЕНИЮ КОГНИТИВНЫХ РАССТРОЙСТВPikhal'skiiA. L.ПухальскийА. Л.
Russian Federation

The authors have indicated they have no financial relationships relevant to this article to disclose.

доктор медицинских наук, профессор, главный научный сотрудник отдела муко- висцидоза МГНЦ Адрес: 115478, Москва, ул. Москворечье, д. 1

info@gabrich.comShmarinaG. V.ШмаринаГ. В.
Russian Federation

MD, leading research scientist of the Department of Cystic fibrosis of Research Centre of Medical Genetics (RCMG)

кандидат медицинских наук, ведущий научный сотрудник отдела муковисцидоза МГНЦ Адрес: 115478, Москва, ул. Москворечье, д. 1, тел.: +7 (499) 612-81-24

osugariver@yahoo.comAleshkinV. A.АлёшкинВ. А.
Russian Federation

PhD, professor, Director of G.N. Gabrichevskii Moscow Research Institute for Epidemiology and Microbiology

доктор биологических наук, профессор, директор МНИИЭМ им. Г.Н. Габричевского

info@gabrich.comResearch Centre for Medical Genetics, Moscow, Russian FederationМедико-генетический научный центр, МоскваResearch Centre for Medical Genetics, MoscowМедико-генетический научный центр, МоскваGabrichevsky Institute of Epidemiology and Microbiology, MoscowМосковский НИИ эпидемиологии и микробиологии им. Г.Н. Габричевского02102014697-8Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук303707082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/405

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitaryadrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and Th17-lymphocyte accumulation) and decreased dehydroepiandrosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, «prompt» (stress hormones) and «delayed» (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion of pro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

При длительном стрессе и при физиологическом старении возникают сходные иммунологические и гормональные нарушения: гиперактивацияи последующее истощение гипоталамо-гипофизарно-надпочечниковой оси, иммунологические нарушения (накопление регуляторных Т-клеток, Treg, и Tх17-лимфоцитов), снижение продукции дегидроэпиандростерона в головном мозге и надпочечниках. Поскольку основные механизмы контроля реакции воспаления (быстрый — гормоны стресса и медленный — Treg) перестают нормально работать, содержание провоспалительных цитокинов в циркуляции может оказаться достаточным, чтобы преодолеть гематоэнцефалический барьер, проницаемость которого существенно возрастает при стрессе и физиологическом старении. В результате циркулирующие в крови цитокины могут проникать в мозг, где начинают выполнять «неиммунологические» функции. Ослабление барьерной функции гематоэнцефалического барьера и развивающаяся нейровоспалительная реакция способствуют массовой миграции дендритных клеток и лимфоцитов из периваскулярного пространства в паренхиму мозга. Вторжение «чуждых» для центральной нервной системы медиаторов и иммунных клеток вызывает развитие когнитивных расстройств как у человека, так и у экспериментальных животных. Предложенная нами концепция развития когнитивного дефицита при стрессе и физиологическом старении позволяет определить главные цели терапии: 1) нормализация численности Treg; 2) компенсация истощения гипоталамо-гипофизарно-надпочечниковой оси; 3) компенсация недостаточности дегидроэпиандростерона; 4) восстановление целостности гематоэнцефалического барьера.

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