IMMUNE DYSFUNCTION АND COGNITIVE DEFICIT IN STRESS AND PHYSIOLOGICAL AGING (PART I): PATHOGENESIS AND RISK FACTORS

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Abstract


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 without
the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term
potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum
cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion
of 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.


About the authors

A. L. Pukhal'skii

Research Centre for Medical Genetics, Moscow, Russian Federation

Email: osugariver@yahoo.com

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.

G. V. Shmarina

Research Centre for Medical Genetics, Moscow

Author for correspondence.
Email: osugariver@yahoo.com

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

V. A. Aleshkin

Gabrichevsky Institute of Epidemiology and Microbiology, Moscow

Email: info@gabrich.com

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

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