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Effects of the Chaperone Inducer U133 on Sleep–Wake Cycle Temporal Characteristics and Spatial Memory

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Abstract

U133, a chaperone inducer synthesized on the basis of echinochrome A, has antitumor, antioxidant and neuroprotective activity. The breadth of its therapeutic effects arouses great interest in this compound as a potential precursor of drugs. However, the functional spectrum of biological activity of U133 remains incomplete. This study aimed to find out whether a U133-induced increase in the chaperone Hsp70 brain level is associated with changes in the sleep–wake cycle and spatial working memory in Wistar rats under natural physiological conditions. Intraperitoneal injection of U133 led to an increase in Hsp70 (HSPA1) levels in the brain structures involved in the mechanisms of sleep–wake cycle regulation and memory formation, such as the locus coeruleus, preoptic area of the hypothalamus, substantia nigra pars compacta, ventral tegmental area of the midbrain). An increase in brain Hsp70 levels was associated with a 1.7-fold increase in the duration of rapid-eye movement sleep (REMS) during the period from the 12th to 24th h after U133 injection, suggesting that the effect of U133 on REMS representation is mediated via Hsp70. Although REMS can affect the formation of different memory modalities, we found no significant effect of U133 on spatial working memory. U133 can be recommended for further investigation of the spectrum of its biological activity in order to predict its therapeutic efficacy in various pathologies of the central nervous system and aging, when sleep is impaired and chaperone expression in the brain is diminished.

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ACKNOWLEDGMENTS

The authors are grateful to Dr. M.A. Gezeyev for his methodological assistance with polysomnographic experiments. Along with biochemical studies, the latter were carried out in the Center for Collective Use at the IEPhB.

Funding

The work was implemented within the state assignment to the IEPhB; theme reg. no. АААА-А18-118012290427-7.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    I. V. Ekimova, N. S. Kurmazov, M. B. Pazi, M. V. Chernyshev & Yu. F. Pastukhov

  2. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia

    S. G. Polonik

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  1. I. V. Ekimova
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  2. N. S. Kurmazov
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  3. M. B. Pazi
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  4. M. V. Chernyshev
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  5. S. G. Polonik
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  6. Yu. F. Pastukhov
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Contributions

Conceptualization and experimental design (I.V.E.); data collection (N.S.K., M.B.P., M.V.Ch.); data analysis (N.S.K., M.B.P., M.V.Ch., Yu.F.P., I.V.E.); rough draft preparation (N.S.K., M.B.P., M.V.Ch.); article writing and editing (I.V.E., Yu.F.P.).

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Correspondence to I. V. Ekimova.

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The authors declare that they have no conflict of interest that would relate to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 8, pp. 984–996https://doi.org/10.31857/S0869813922080027.

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Ekimova, I.V., Kurmazov, N.S., Pazi, M.B. et al. Effects of the Chaperone Inducer U133 on Sleep–Wake Cycle Temporal Characteristics and Spatial Memory. J Evol Biochem Phys 58, 1214–1224 (2022). https://doi.org/10.1134/S002209302204024X

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