Skip to main content
Log in

Effect of Lighting Regimes and the Melatonin Receptor Antagonist Luzindole on the Composition of Peripheral Blood Leukocytes of Wistar Rats in Postnatal Ontogenesis

  • Published:
Advances in Gerontology Aims and scope Submit manuscript

Abstract

A study of hematological parameters in postnatal ontogenesis was carried out on 151 Wistar rats (74 males and 77 females) kept during embryonic development and after birth in either standard lighting conditions (LD, 12 : 12) or in complete darkness (DD). The age, photoperiod, and the melatonin-receptor antagonist luzindole had a significant effect on the composition of peripheral blood leukocytes. The age-related changes in the values of the studied parameters consisted of a decrease in the total amount of leukocytes and the relative content of lymphocytes and an increase in the neutrophil level. The age-related decrease in the number of leukocytes, and lymphocytes slowed, and the level of large granular lymphocytes (LGLs) was lower, on average, in the conditions of light deprivation as compared with LD regime. The effect of luzindole depended on the lighting conditions and age: the preparation increased the lymphocyte number and decreased the neutrophil level in DD in old rats (24 months) and decreased the LGL content in LD. Apparently, luzindole affects the relative content of different types of white blood cells in the peripheral blood via melatonin receptors or other immunoregulatory mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

REFERENCES

  1. Anisimov, V.N. and Vinogradova, I.A., Light regime, melatonin, and cancer risk, Vopr. Onkol., 2006, vol. 52, no. 5, pp. 491–498.

    CAS  PubMed  Google Scholar 

  2. Doronin, V.A., Nikitin, E.A., Sidorova, Yu.V., and Pivnik, A.V., Neutropenia in rheumatoid arthritis and large granular lymphocyte leucosis, Nauchno-Prakt. Revmatol., 2003, no. 1, pp. 15–18.

  3. Zhukova, O.V., Obukhova, E.S., Khizhkin, E.A., et al., Luzindole accelerates the aging of estrous function of female rats, Adv. Gerontol., 2016, vol. 6, no. 4, pp. 322–327.

    Article  Google Scholar 

  4. Kosyreva, A.M., Makarova, O.V., and Osmolovs-kaya, E.Yu., Age-related features and sex-related differences in morphofunctional changes in the thymus of Wistar rats with a systemic inflammatory response, Klin. Eksp. Morfol., 2016, no. 1, pp. 18–26.

  5. Novozhilov, A.V. and Katyukhin, L.N., Dynamics of hematological blood parameters of white rats in postnatal ontogenesis, J. Evol. Biochem. Physiol., 2008, vol. 44, no. 6, pp. 724–734.

    Article  Google Scholar 

  6. Sigidin, Ya.A., Lukina, G.V., and Posdnyakova, E.S., Felty syndrome and large granular leukocyte T-cell leukemia—a natural combination, Nauchno-Prakt. Revmatol., 2007, no. 3, pp. 105–108.

  7. Uzenbaeva, L.B., Vinogradova, I.A., Kizhina, A.G., et al., Influence of melatonin on neutrophil-to-lymphocyte ratio in mammalian blood depending on age of the animal, Adv. Gerontol., 2013, vol. 3, no. 1, pp. 61–66.

    Article  Google Scholar 

  8. Khizhkin, E.A., Yunash, V.D., Ilyukha, V.A., et al., Reproduction and puberty in rats exposed to constant darkness, Tr. Karel. Nauchn. Tsentra, Ross. Akad. Nauk, 2014, no. 5, pp. 200–206.

  9. Khizhkin, E.A., Gulyavina, A.V., Ilyukha, V.A., et al., Age-related changes in the behavior and phobic anxiety reactions in rats under exposure to light deprivation and luzindole, Tr. Karel. Nauchn. Tsentra, Ross. Akad. Nauk, 2018, no. 12, pp. 110–124.

  10. Eticheskaya ekspertiza biomeditsinskikh issledovanii: Prakticheskie rekomendatsii (Ethical Expertise of Biomedical Studies: Practical Recommendations), Belousov, Yu.B., Ed., Moscow, 2005.

    Google Scholar 

  11. Abo, T., Cooper, M.D., and Balch, C.M., Postnatal expansion of the natural killer and keller cell population in humans identified by the monoclonal HNK-1 antibody, J. Exp. Med., 1982, vol. 155, no. 1, pp. 321–326.

    Article  CAS  PubMed  Google Scholar 

  12. Aspinall, R., Longevity and the immune response, Biogerontology, 2000, vol. 1, pp. 273–278.

    Article  CAS  PubMed  Google Scholar 

  13. Bash, J.A. and Vogel, D., Cellular immunosenescence in F344 rats: decreased natural killer (NK) cell activity involves changes in regulatory interactions between NK cells, interferon, prostaglandin and macrophages, Mech. Ageing Dev., 1984, vol. 24, no. 1, pp. 49–65.

    Article  CAS  PubMed  Google Scholar 

  14. Born, J., Uthgenannt, D., Dodt, C., et al., Cytokine production and lymphocyte subpopulations in aged humans. An assessment during nocturnal sleep, Mech. Ageing Dev., 1995, vol. 84, pp. 113–126.

    Article  CAS  PubMed  Google Scholar 

  15. Brittenden, J., Heys, S.D., Ross, J., and Eremin, O., Natural killer cells and cancer, Cancer, 1996, vol. 77, pp. 1226–1243.

    Article  CAS  PubMed  Google Scholar 

  16. Butcher, S.K. and Lord, J.M., Stress responses and innate immunity: aging as a contributory factor, Aging Cell, 2004, vol. 3, no. 4, pp. 151–160.

    Article  CAS  PubMed  Google Scholar 

  17. Calvo, J.R., Gonzalez-Yanes, C., and Maldonado, M.D., The role of melatonin in the cells of the innate immunity, J. Pineal Res., 2013, vol. 55, pp. 103–120.

    Article  CAS  PubMed  Google Scholar 

  18. Cheng, M., Zhang, J., Jiang, W., et al., Natural killer cell lines in tumor immunotherapy, Front. Med., 2012, vol. 6, no. 1, pp. 56–66.

    Article  PubMed  Google Scholar 

  19. Constantinescu, C.S., Hilliard, B., Ventura, E., and Rostami, A., Luzindole, a melatonin receptor antagonist, suppresses experimental autoimmune encephalomyelitis, Pathobiology, 1997, vol. 65, pp. 190–194.

    Article  CAS  PubMed  Google Scholar 

  20. Currier, N., Sun, L.Z.Y., and Miller, S., Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity, J. Neuroimmunol., 2000, vol. 104, no. 2, pp. 101–108.

    Article  CAS  PubMed  Google Scholar 

  21. Dalbeth, N., Gundle, R., Davies, R.J., et al., CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation, J. Immunol., 2004, vol. 173, no. 10, pp. 6418–6426.

    Article  CAS  PubMed  Google Scholar 

  22. Díaz López, B., Díaz Rodríguez, E., Colmenero, M.D., et al., Maternal melatonin influences rates of somatic and reproductive organs postnatal development of male rat offspring, Neuro Endocrinol. Lett., 1999, vol. 20, pp. 69–76.

  23. Drazen, D.L., Bilu, D., Bilbo, S.D., and Nelson, R.J., Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist, Am. J. Physiol.: Regul. Integr. Comp. Physiol., 2001, vol. 280, no. 5, pp. 1476–1482.

    Google Scholar 

  24. Dubocovich, M.L., Mogilnicka, E., and Areso, P.M., Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test, Eur. J. Pharmacol., 1990, vol. 182, no. 2, pp. 313–325.

    Article  CAS  PubMed  Google Scholar 

  25. Dubocovich, M.L. and Markowska, M., Functional MT1 and MT2 melatonin receptors in mammals, Endocrine, 2005, vol. 27, no. 2, pp. 101–110.

    Article  CAS  PubMed  Google Scholar 

  26. Grégoire, C., Chasson, L., Luci, C., et al., The trafficking of natural killer cells, Immunol. Rev., 2007, vol. 220, pp. 169–182.

  27. Hannet, I., Erkeller-Yuksel, F., Lydyard, P., et al., Developmental and maturational changes in human blood lymphocyte subpopulations, Immunol. Today, 1992, vol. 13, no. 6, pp. 215–218.

    Article  CAS  PubMed  Google Scholar 

  28. Hu, D. and Miller, R., Evidence of a lineage shift between natural (NK) killer cells and T lymphocytes in the spleen and blood of neonatally thymectomized, young adult C3H mice, Curr. Pediatr. Res., 2014, vol. 18, no. 1, pp. 43–47.

    Google Scholar 

  29. Lewiński, A., Zelazowski, P., Sewerynek, E., et al., Melatonin-induced suppression of human lymphocyte natural killer activity in vitro, J. Pineal Res., 1989, vol. 7, pp. 153–164.

  30. Lotufo, C.M., Lopes, C., Dubocovich, M.L., et al., Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation, Eur. J. Pharmacol., 2001, vol. 430, nos. 2–3, pp. 351–357.

  31. Lotzová, E., Natural killer cells: immunobiology and clinical prospects, Cancer Invest., 1991, vol. 9, no. 2, pp. 173–184.

  32. Maestroni, G.J.M., The immunotherapeutic potential of melatonin, Expert Opin. Invest. Drugs, 2001, vol. 10, no. 3, pp. 467–476.

    Article  CAS  Google Scholar 

  33. Mahmoud, I., Salman, S.S., and Al-Khateeb, A., Continuous darkness and continuous light induce structural changes in the rat thymus, J. Anat., 1994, vol. 185, no. 1, pp. 143–149.

    PubMed  PubMed Central  Google Scholar 

  34. Mandal, A. and Viswanathan, C., Natural killer cells: In health and disease, Hematol. Oncol. Stem Cell Ther., 2015, vol. 8, no. 2, pp. 47–55.

    Article  PubMed  Google Scholar 

  35. Martin-Cacao, A., Lopez-Gonzalez, M.A., Reiter, R.J., et al., Binding of 2-[125I] melatonin by rat thymus membranes during postnatal development, Immunol. Lett., 1993, vol. 36, pp. 59–64.

    Article  CAS  PubMed  Google Scholar 

  36. Michel, T., Poli, A., Cuapio, A., et al., Human CD56bright NK cells: an update, J. Immunol., 2016, vol. 196, no. 7, pp. 2923–2931.

    Article  CAS  PubMed  Google Scholar 

  37. Mocchegiani, E. and Malavolta, M., NK and NKT cell functions in immunosenescence, Aging Cell, 2004, vol. 3, no. 4, pp. 177–184.

    Article  CAS  PubMed  Google Scholar 

  38. Nogusa, S., Ritz, B.W., Kassim, S.H., et al., Characterization of age-related changes in natural killer cells during primary influenza infection in mice, Mech. Ageing Dev., 2008, vol. 129, pp. 223–230.

    Article  CAS  PubMed  Google Scholar 

  39. Peng, H. and Tian, Z., Diversity of tissue-resident NK cells, Semin. Immunol., 2017, vol. 31, pp. 1–8.

    Article  Google Scholar 

  40. Pross, H.F. and Baines, M.G., Studies of human natural killer cells. I. in vivo parameters affecting normal cytotoxic function, Int. J. Cancer, 1982, vol. 29, pp. 383–390.

    Article  CAS  PubMed  Google Scholar 

  41. Provinciali, M., Di Stefano, G., Bulian, D., et al., Long-term melatonin supplementation does not recover the impairment of natural killer cell activity and lymphocyte proliferation in aging mice, Life Sci., 1997, vol. 61, no. 9, pp. 857–864.

    Article  CAS  PubMed  Google Scholar 

  42. Requintina, P.J. and Oxenkrug, G.F., Effect of luzindole and other melatonin receptor antagonists on iron- and lipopolysaccharide-induced lipid peroxidation in vitro, Ann. N.Y. Acad. Sci., 2007, vol. 1122, pp. 289–294.

    Article  CAS  PubMed  Google Scholar 

  43. Robertson, M.J. and Ritz, J., Biology and clinical relevance of human natural killer cells, Blood, 1990, vol. 176, no. 12, pp. 2421–2438.

    Article  Google Scholar 

  44. Sansoni, P., Brianti, V., Fagnoni, F., et al., NK cell activity and T-lymphocyte proliferation in healthy centenarians, Ann. N.Y. Acad. Sci., 1992, vol. 663, pp. 505–507.

    Article  CAS  PubMed  Google Scholar 

  45. Slominski, R.M., Reiter, R.J., Schlabritz-Loutsevitch, N., et al., Melatonin membrane receptors in peripheral tissues: distribution and functions, Mol. Cell Endocrinol., 2012, vol. 351, no. 2, pp. 152–166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sun, J.C. and Lanier, L.L., NK cell development, homeostasis and function: parallels with CD8+ T cells, Nat. Rev. Immunol., 2011, vol. 11, no. 10, pp. 645–657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tsukamoto, H., Clise-Dwyer, K., Huston, G.E., et al., Age-associated increase in lifespan of naive CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects, Proc. Natl. Acad. Sci. U.S.A., 2009, vol. 106, no. 43, pp. 18 333–18 338.

    Article  Google Scholar 

  48. Viveros, M.P., Arranz, L., Hernanz, A., et al., A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence, Neuroimmunomodulation, 2007, vol. 14, nos. 3–4, pp. 157–162.

  49. Wajs, E., Kutoh, E., and Gupta, D., Melatonin affects proopiomelanocortin gene expression in the immune organs of the rat, Eur. J. Endocrinol., 1995, vol. 133, pp. 754–760.

    Article  CAS  PubMed  Google Scholar 

  50. Wolford, S.T., Schroer, R.A., Gallo, P.P., et al., Age-related changes in serum chemistry and hematology values in normal Sprague–Dawley rats, Fundam. Appl. Toxicol., 1987, vol. 1, pp. 80–88.

    Article  Google Scholar 

Download references

Funding

This work was supported by the federal budget for the implementation of state task no. 0218-2019-0073.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. B. Uzenbaeva.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. The studies were carried out in compliance with the international principles of the E.U. Directive on the humane treatment of animals and rules for working with experimental animals [10]. The experiment was approved by the independent Committee on Bioethics of the Institute of Biology, Karelian Research Center, Russian Academy of Sciences, according to the protocol dated October 3, 2016.

Additional information

Translated by A. Barkhash

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uzenbaeva, L.B., Kizhina, A.G., Kalinina, S.N. et al. Effect of Lighting Regimes and the Melatonin Receptor Antagonist Luzindole on the Composition of Peripheral Blood Leukocytes of Wistar Rats in Postnatal Ontogenesis. Adv Gerontol 11, 164–172 (2021). https://doi.org/10.1134/S2079057021020156

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079057021020156

Keywords:

Navigation