Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC42310.15690/vramn.v69i5-6.1038РATHOPHYSIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ПАТОФИЗИОЛОГИИIMMUNE DYSFUNCTION АND COGNITIVE DEFICIT IN STRESS AND PHYSIOLOGICAL AGING (PART I): PATHOGENESIS AND RISK FACTORSИММУНОЛОГИЧЕСКИЕ НАРУШЕНИЯ И КОГНИТИВНЫЙ ДЕФИЦИТ ПРИ СТРЕССЕ И ФИЗИОЛОГИЧЕСКОМ СТАРЕНИИ. ЧАСТЬ I: ПАТОГЕНЕЗ И ФАКТОРЫ РИСКАPukhal'skiiA. L.ПухальскийА. Л.
Russian Federation

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.

osugariver@yahoo.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

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

PhD, professor, Director of G.N.Gabrichevskii Moscow Research Institute of 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, Москва, Российская ФедерацияResearch Centre for Medical Genetics, MoscowМедико-генетический научный центр, МоскваGabrichevsky Institute of Epidemiology and Microbiology, MoscowМосковский НИИ эпидемиологии и микробиологии им. Г.Н. Габричевского01102014695-6Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук142207082015Copyright ©; 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/423

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets.The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines withoutthe intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-termpotentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serumcytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusionof biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments.In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

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.

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