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The Role of Alpha-Tocopherol and Cycloferon in the Regulation of Apoptosis in Neurons of the Hypothalamic Suprachiasmatic Nucleus and Pinealocytes during Stress and Aging

  • Morphological Basics for Evolution of Functions
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Abstract

The suprachiasmatic nucleus (SCN) of the hypothalamus and the pineal gland (epiphysis) play an important role not only in the regulation of circadian rhythms but also in the implementation of adaptive responses, including those to various stress factors. Age-related morphofunctional changes in these brain structures, including those associated with increased oxidative stress, exert a significant effect on the organism as a whole. The aim of this work was to explore the dynamics and mechanism of apoptosis in pinealocytes and SCN neurosecretory cells as well as to determine the possibilities of pharmacological correcting this process by an antioxidant alpha-tocopherol and an immunomodulator cycloferon under physiological and immobilization stress conditions in young (2–4-month-old) and aged (30-month-old) Wistar rats. The preparations were administered perorally once a day for 14 days. While the apoptosis level increased with age both in the SCN and the pineal gland, administration of alpha-tocopherol, cycloferon and their combination led to abate this process. It was shown that stress-induced apoptosis in the SCN and the pineal gland proceeds via the p53-dependent pathway, while administration of alpha-tocopherol acetate, cycloferon and their combination decreases the apoptosis level in pinealocytes, suppressing p53 expression both in young and aged animals. In the SCN, no relationship was found between apoptosis and p53 expression levels after administration of the above preparations during stress, suggesting the involvement of different mechanisms.

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Funding

This work was implemented within the state as-signment;theme no. AAAA-A18-118012290371-3.

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Authors and Affiliations

  1. Astrakhan State Medical University, Astrakhan, Russia

    L. K. Khuzhakhmetova

  2. Astrakhan State University, Astrakhan, Russia

    D. L. Teply & E. D. Bazhanova

  3. Institute of Toxicology, Federal Medical and Biological Agency of Russia, St. Petersburg, Russia

    M. M. Belyaeva & E. D. Bazhanova

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

    E. D. Bazhanova

Authors
  1. L. K. Khuzhakhmetova
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  2. M. M. Belyaeva
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  3. D. L. Teply
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  4. E. D. Bazhanova
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Corresponding author

Correspondence to E. D. Bazhanova.

Ethics declarations

All experiment were carried out in compliance with the National Standard of the Russian Federation P-53434-2009 entitled “Principles of good laboratory practice” and the appropriate Order of the Russian Federation Ministry of Health no. 199n of 01.04.2016.

This study did not involve human subjects as research objects.

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Russian Text © The Author(s), 2019, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2019, Vol. 55, No. 5, pp. 331–338.

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Khuzhakhmetova, L.K., Belyaeva, M.M., Teply, D.L. et al. The Role of Alpha-Tocopherol and Cycloferon in the Regulation of Apoptosis in Neurons of the Hypothalamic Suprachiasmatic Nucleus and Pinealocytes during Stress and Aging. J Evol Biochem Phys 55, 380–387 (2019). https://doi.org/10.1134/S0022093019050053

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  • DOI: https://doi.org/10.1134/S0022093019050053

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