Molecular mechanisms of neuroinflammation and sleep deprivation in the development of age-associated cognitive dysfunction

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Abstract

Introduction. Proinflammatory cytokines produced in elevated concentrations in the elderly significantly impair neurogenesis in the dentate gyrus of the hippocampus, long-term potentiality, alter neuronal morphology and function, and increase apoptosis. This leads to impaired episodic memory, executive function, and spatial learning, as well as neurodegeneration. Half of the elderly suffer from sleep disorders. Insomnia causes activation of microglia and increases 24-hour expression of proinflammatory cytokines, which enhances pre-existing inflammation, which in turn exacerbates insomnia.

Objective: to systematize scientific data on the role of sleep disorders in the development of neuroinflammation in the elderly, other causes and consequences of this condition, as well as on methods of insomnia correction in the elderly.

Material and methods: an analysis of the main foreign and domestic sources from PubMed/Medline, elibrary.ru databases was performed.

Conclusion. Aging is associated with the inevitable accumulation of cellular damage and depletion of endogenous mechanisms to eliminate DAMPs. Their excessive amount excessively activates NLRP3 inflammasome expressing proinflammatory cytokines. Chronic sleep deprivation in aging occurs because of disturbances in the interaction between sleep homeostatic mechanisms and circadian clock parameters, resulting in increased levels of proinflammatory cytokines. Increased levels of neuroinflammation impair the survival and proliferation of new neurons and their proper integration into pre-existing hippocampal neural networks encoding spatial information. Increased apoptosis, impaired gliogenesis, dendritic atrophy, and loss of synapses also contribute to the decreased size of the hippocampus in sleep disorders.

The use of behavioral strategies to improve sleep quality in the elderly (sleep hygiene, moderate exercise, and social activity) has been discussed to correct the negative effects of chronic neuroinflammation.

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About the authors

Kristina E. Nazarova

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Departament of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry

Email: krisnaz@mail.ru
ORCID iD: 0000-0002-3797-172X

student of Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Russian Federation, Partizana Zheleznyaka str., 1Z, Krasnoyarsk, 660022

Regina A. Kostromina

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Departament of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry

Email: regina.kostromina@mail.ru
ORCID iD: 0000-0001-7406-7900

student of Professor V.F. Voino–Yasenetsky Krasnoyarsk State Medical University

Russian Federation, Partizana Zheleznyaka str., 1Z, Krasnoyarsk, 660022

Nataliya A. Malinovskaya

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Departament of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry

Email: malinovskaya-na@mail.ru
ORCID iD: 0000-0002-0033-3804

head of the Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, doctor of Medical Sciences

Russian Federation, Partizana Zheleznyaka str., 1Z, Krasnoyarsk, 660022

Elena D. Khilazheva

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Departament of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry

Email: elena.hilazheva@mail.ru
ORCID iD: 0000-0002-9718-1260

senior lecturer of the Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Russian Federation, Partizana Zheleznyaka str., 1Z, Krasnoyarsk, 660022

Yulia K. Komleva

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Departament of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry

Author for correspondence.
Email: yuliakomleva@mail.ru
ORCID iD: 0000-0001-5742-8356

professor of the Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry Professor V.F. Voino–Yasenetsky Krasnoyarsk State Medical University, doctor of Medical Sciences, assistant professor

Russian Federation, Partizana Zheleznyaka str., 1Z, Krasnoyarsk, 660022

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2. Fig. 1. Mechanisms leading to increased activation of inflammasomes in an aging body

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3. Fig. 3. The effect of chronic sleep disorders on the processes of inflammation in the brain in the elderly

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4. Fig. 2. Peculiarities of the sleep-wake cycle in physiological aging Note. REM – rapid eye movement sleep; NREM – nonrapid eye movement sleep; SWS – slow-wave sleep (N3 stage of NREM sleep).

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