Effect of glyproline neuropeptides on the level of interleukins and neurotrophic factors under stress

• Anna L. Yasenyavskaya
• Alexandra A. Tsybizova
• Lyudmila A. Andreeva
• Nikolay F. Myasoedov
• Olga A. Bashkina
• Marina A. Samotrueva

Abstract

Introduction. At present, scientific works are giving special results, reflecting the study of the pathological impact of stress factors, including those of a social nature, on various systems of the body. Stress effect in biochemical terms is manifested by the release of glucocorticoids in the blood, referring this process to one of the main levers of influence on the immune system by changing the secretion of pro-inflammatory and anti-inflammatory cytokines by immunocytes. Currently, close attention is paid to the assessment of the role of interleukins, neurotrophic factors and other cytokines in the implementation of the stress response, as well as the search for means of correcting these disorders.

The aim – to study the effect of glyproline compounds on the level of interleukins (IL-1β and IL-6) and neurotrophic (NGF and BDNF) factors in the blood serum of white rats on a model of social stress.

Material and methods. Experimental studies were carried out on 90 nonlinear white male rats of 6 months of age. The maintenance of laboratory animals met the requirements of international and domestic regulatory documentation on working with animals. In the process of modeling social stress, all rats were divided by type of behavior to aggressors and victims. Experimental groups (n = 10) were formed in the study: control animals; animals exposed to stress for 20 days; groups of rats treated intraperitoneally at a dose of 100 mcg/kg in day, starting from the 1st day of stress factor exposure, with a course of 20 days neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro, Pro–Gly–Pro–Leu. The levels of interleukins and neurotrophic factors in the blood serum of white rats were evaluated by enzyme immunoassay.

Results. According to the results of the study, it was found that under conditions of social stress, there was an increase in the concentration of pro-inflammatory interleukins and a decrease in the concentration of BDNF and NGF. The introduction of neuropeptide compounds against the background of stress contributed to the restoration of the level of the studied indicators, which is most likely due to the presence of neuropeptides of neuroprotective action due to the induction of the synthesis of neurotrophic factors.

Conclusion. Thus, the introduction of glyproline compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro, Pro–Gly–Pro and Pro–Gly–Pro–Leu under stress conditions contributes to the restoration of levels of interleukins and neurotrophic factors, as a result of which the stress- and neuroprotective effect of the studied compounds is observed.

Keywords:neuropeptides; social stress; neurogenic inflammation, interleukins, brain neurotrophic factor; nerve growth factor

References

1. Benham G., Charak R. Stress and sleep remain significant predictors of health after controlling for negative affect. Stress Health. 2019; 35 (1): 59–68. DOI: https://doi.org/10.1002/smi.2840

2. Cohen S., Gianaros A.P.J., Manuck S.B. Stage model of stress and disease. Perspect. Psychol. Sci. 2016; 11 (4): 56–63. DOI: https://doi.org/10.1177/1745691616646305

3. Zaytseva N.S., Sizyakina L.P. The role of innate immunity factors in the formation of adaptive reactions under stress. Immunologiya. 2021; 42 (3): 270–6. DOI: https://doi.org/10.33029/0206-4952-2021-42-3-270-276 (in Russian)

4. O’Connor D.B., Thayer J.F., Vedhara K. Stress and health: a review of psychobiological processes. Annu. Rev. Psychol. 2021; 72: 663–88. DOI: https://doi.org/10.1146/annurev-psych-062520-122331

5. Kuznik B.I., Davydov S.O., Landa I.V. Nerve growth factor (NGF) and its role in the conditions of norm and pathology. Uspekhi fiziologicheskikh nauk. 2019; 50 (4): 64–80. (in Russian)

6. Santucci D., Racca A., Alleva E. When nerve growth factor met behavior. Adv. Exp. Med. Biol. 2021; 1331: 205–14. DOI: https://doi.org/10.1007/978-3-030-74046-7_13

7. Kryzhanovskaya S.Yu., Zapara M.A., Glazachev O.S. Neurotrophins and adaptation to environmental stimuli: possibilities of expanding the «therapeutic potential» (a brief overview). Vestnik mezhdunarodnoy akademii nauk (Russkaya sektsiya). 2020; 1: 36–43. (in Russian)

8. Levchuk L.A., Vyalova N.M., Mikhalitskaya E.V., et al. The role of BDNF in the pathogenesis of neurological and mental disorders. Sovremennye problemy nauki i obrazovaniya. 2018; 6: 58. URL: https://science-education.ru/ru/article/view?id=28267 (in Russian)

9. Islands I.V., Golubeva N.V., Kuzovlev A.N., et al. Prognostic significance and therapeutic potential of brain neurotrophic factor BDNF in brain damage (review). Obshchaya reanimatologiya. 2019; 15 (1): 70–86. DOI: https://doi.org/10.15360/1813-9779-2019-1-70-86 (in Russian)

10. Duman R.S., Deyama S., Fogaça M.V. Role of BDNF in the pathophysiology and treatment of depression: activity-dependent effects distinguish rapid-acting antidepressants. Eur. J. Neurosci. 2021; 53 (1): 126–39. DOI: https://doi.org/10.1111/ejn.14630.

11. Carr R., Frings S. Neuropeptides in sensory signal processing. Cell Tissue Res. 2019; 375 (1): 217–25. DOI: https://doi.org/10.1007/s00441-018-2946-3

12. Kanunnikova N.P. Neuroprotective properties of neuropeptides. J. Grodno State Med. Univ. 2017; 15 (5): 492–8. DOI: https://doi.org/10.25298/2221-8785-2017-15-5-492-498

13. Samotrueva M.A., Yasenyavskaya A.L., Murtalieva V.K., et al. Experimental Substantiation of application of semax as a modulator of immune reaction on the model of «social» stress. Bull. Exp. Biol. Med. 2019; 166 (6): 754–8. DOI: https://doi.org/10.1007/s10517-019-04434-y

14. Vyunova T.V., Andreeva L.A., Shevchenko K.V., et al. An integrated approach to study the molecular aspects of regulatory peptides biological mechanism. J. Labelled Comp. Radiopharm. 2019; 62 (12): 812–22. DOI: https://doi.org/10.1002/jlcr.3785

15. Avgustinovich D.F., Kovalenko I.L., Kudryavtseva N.N. A model of anxious depression: persistence of behavioral pathology. Neurosci. Behav. Physiol. 2005; 35 (9): 917–24. DOI: https://doi.org/10.1007/s11055-005-0146-6

16. Koolhaas J.M., De Boer S.F., Buwalda B., et al. Social stress models in rodents: Towards enhanced validity. Neurobiol. Stress. 2017; 6: 104–12. DOI: https://doi.org/10.1016/j.ynstr.2016.09.003

17. Yasenyavskaya A.L., Samotrueva M.A., Myasoedov N.F., et al. The effect of semax on the level of interleukin-1ß in conditions of «social» stress. Meditsinskiy akademicheskiy zhurnal. 2019; 9 (S): 192–4. DOI: https://doi.org/10.17816/MAJ191S1192-194 (in Russian)

18. Fricker L.D. Carboxypeptidase E and the identification of novel neuropeptides as potential therapeutic targets. Adv. Pharmacol. 2018; 82: 85–102. DOI: https://doi.org/10.1016/bs.apha.2017.09.001

19. Thiele T.E. Neuropeptides and addiction: an introduction. Int. Rev. Neurobiol. 2017; 136: 1–3. DOI: https://doi.org/10.1016/bs.irn.2017.07.001

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