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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.

About the authors

A. L. Pikhal'skii

Research Centre for Medical Genetics, Moscow, Russian Federation

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

G. V. Shmarina

Research Centre for Medical Genetics, Moscow

Author for correspondence.
MD, leading research scientist of the Department of Cystic fibrosis of Research Centre of Medical Genetics (RCMG) Russian Federation

V. A. Aleshkin

Gabrichevsky Institute of Epidemiology and Microbiology, Moscow


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



Russian Federation


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