Длительная социальная изоляция приводит к снижению экспрессии предшественника BDNF и пролилэндопептидазы в структурах мозга крыс

Сноски

* Адресат для корреспонденции.

Финансирование

Работа выполнена при финансовой поддержке Российского фонда фундаментальных исследований (грант № 20-315-90110) и государственного задания ФГБНУ «Научно-исследовательский институт общей патологии и патофизиологии (рег. № НИОКТР АААА-А19-119100790089-5).

Благодарности

Авторы выражают благодарность доктору биологических наук Юлии Игоревне Кировой за консультации и помощь в проведении исследований методом иммуноблоттинга.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Все процедуры и эксперименты на животных проводили в соответствии с «Правилами надлежащей лабораторной практики», утверждёнными приказом Министерства здравоохранения РФ № 199н от 01.04.2016, и ГОСТ 33215-2014, 33216-2014 «Руководство по содержанию и уходу за лабораторными животными» под контролем Этического комитета ФГБНУ «НИИОПП» (протокол утверждения проекта исследования № 6 от 23.11.2018, протокол окончательного утверждения проведённого исследования № 3 от 16.06.2020). Все применимые международные, национальные и/или институциональные принципы ухода и использования животных были соблюдены.

Дополнительные материалы

Приложение к статье на английском языке опубликовано на сайте журнала «Biochemistry» (Moscow) (http://protein.bio.msu.ru/biokhimiya/) и на сайте издательства Springer (https://link.springer.com/journal/10541), том 86, вып. 6, 2021.

Список литературы

1. Walker, A. J., Kim, Y., Price, J. B., Kale, R. P., McGillivray, J. A., et al. (2014) Stress, inflammation, and cellular vulnerability during early stages of affective disorders: biomarker strategies and opportunities for prevention and intervention, Front. Psychiatry, 5, 34, doi: 10.3389/fpsyt.2014.00034.

2. Vargas, J., Junco, M., Gomez, C., and Lajud, N. (2016) Early life stress increases metabolic risk, HPA axis reactivity, and depressive-like behavior when combined with postweaning social isolation in rats, PLoS One, 11, e0162665, doi: 10.1371/journal.pone.0162665.

3. Friedler, B., Crapser, J., and McCullough, L. (2015) One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition, Acta Neuropathol., 129, 493-509, doi: 10.1007/s00401-014-1377-9.

4. Duffy, K. A., McLaughlin, K. A., and Green, P. A. (2018) Early life adversity and health-risk behaviors: proposed psychological and neural mechanisms, Ann. N. Y. Acad. Sci., 1428, 151-169, doi: 10.1111/nyas.13928.

5. Mumtaz, F., Khan, M. I., Zubair, M., and Dehpour, A. R. (2018) Neurobiology and consequences of social isolation stress in animal model – a comprehensive review, Biomed. Pharmacother., 105, 1205-1222, doi: 10.1016/j.biopha.2018.05.086.

6. Schweinfurth, M. K. (2020) The social life of Norway rats (Rattus norvegicus), Elife, 9, e54020, doi: 10.7554/eLife.54020.

7. Fone, K. C., and Porkess, M. V. (2008) Behavioural and neurochemical effects of post-weaning social isolation in rodents – relevance to developmental neuropsychiatric disorders, Neurosci. Biobehav. Rev., 32, 1087-1102, doi: 10.1016/j.neubiorev.2008.03.003.17.

8. Liu, N., Wang, Y., An, A. Y., Banker, C., Qian, Y.-H., and O’Donnell, J. M. (2020) Single housing-induced effects on cognitive impairment and depression-like behavior in male and female mice involve neuroplasticity-related signaling, Eur. J. Neurosci., 52, 2694-2704, doi: 10.1111/ejn.14565.

9. Siuda, D., Wu, Z., Chen, Y., Guo, L., Linke, M., et al. (2014) Social isolation-induced epigenetic changes in midbrain of adult mice, J. Physiol. Pharmacol., 65, 247-255.

10. Murgatroyd, C., Patchev, A., Wu, Y., Micale, V., Bockmühl, Y., et al. (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress, Nat. Neurosci., 12, 1559-1566, doi: 10.1038/nn.2436.

11. Gapp, K., von Ziegler, L., Tweedie-Cullen, R Y., and Mansuy, I. M. (2014) Early life epigenetic programming and transmission of stress-induced traits in mammals, BioEssays, 36, 491-502, doi: 10.1002/bies.201300116.

12. Gulyaeva, N. V. (2017) Molecular mechanisms of neuroplasticity: an expanding universe, Biochemistry (Moscow), 82, 237-242, doi: 10.1134/S0006297917030014.

13. Korzhevskii, D. E., Petrova, E. S., Kirik, O. V., Beznin, G. V., and Sukhrukova, E. G. (2010) Neural markers used for investigation of differentiation of stem cells, Geny Kletki, 5, 57-63.

14. Kolos, E. A., Grigoriev, I. P., and Korzhevskii, D. E. (2015) Marker of synaptic contacts – synaptophisin, Morfologiya, 147, 79-83.

15. Hao, Y., Shabanpoor, A., and Metz, G. A. (2017) Stress and corticosterone alter synaptic plasticity in a rat model of Parkinson’s disease, Neurosci. Lett., 651, 79-87, doi: 10.1016/j.neulet.2017.04.063.

16. Xu, H., He, J., Richardson, J. S., and Li, X. M. (2004) The response of synaptophysin and microtubule-associated protein 1 to restraint stress in rat hippocampus and its modulation by venlafaxine, J. Neurochem., 91, 1380-1388, doi: 10.1111/j.1471-4159.2004.02827.x.

17. Gemmel, M., Kokras, N., Dalla, C., and Pawluski, J. L. (2018) Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring, Neuropharmacology, 128, 68-180, doi: 10.1016/j.neuropharm.2017.10.009.

18. Zhang, L., Luo, J., Zhang, M., Yao, W., Ma, X., and Yu, S. Y. (2014) Effects of curcumin on chronic, unpredictable, mild, stress-induced depressive-like behaviour and structural plasticity in the lateral amygdala of rats, Int. J. Neuropsychopharmacology, 17, 793-806, doi: 10.1017/S1461145713001661.

19. Hescham, S., Grace, L., Kellaway, L. A., Bugarith, K., and Russell, V. A. (2009) Effect of exercise on synaptophysin and calcium/calmodulin-dependent protein kinase levels in prefrontal cortex and hippocampus of a rat model of developmental stress, Metab. Brain Dis., 24, 701-709, doi: 10.1007/s11011-009-9165-2.

20. Andersen, S. L., and Teicher, M. H. (2004) Delayed effects of early stress on hippocampal development, Neuropsychopharmacology, 29, 1988-1993, doi: 10.1038/sj.npp.1300528.

21. Dandi, Е., Kalamari, A., Touloumi, O., Lagoudaki, R., Nousiopoulou, E., et al. (2018) Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress, Int. J. Dev. Neurosci., 67, 19-32, doi: 10.1016/j.ijdevneu.2018.03.003.

22. Ramos-Ortolaza, D. L., Doreste-Mendez, R. J., Alvarado-Torres, J. K., and Torres-Reveron, A. (2017) Ovarian hormones modify anxiety behavior and glucocorticoid receptors after chronic social isolation stress, Behav. Brain Res., 328, 115-122, doi: 10.1016/j.bbr.2017.04.016.

23. Varty, G. B., Marsden, C. A., and Higgins, G. A. (1999) Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats, Brain Res., 824, 197-203, doi: 10.1016/s0006-8993(99)01173-7.

24. Das, S. K., Baitharu, I., Barhwal, K., Hota, S. K., and Singh, S. B. (2016) Early mood behavioral changes following exposure to monotonous environment during isolation stress is associated with altered hippocampal synaptic plasticity in male rats, Neurosci. Lett., 612, 231-237, doi: 10.1016/j.neulet.2015.12.038.

25. Bondar, N. P., and Merkulova, T. I. (2016) Brain-derived neurotrophic factor and early-life stress: Multifaceted interplay, J. Biosci., 41, 751-758, doi: 10.1007/s12038-016-9648-3.

26. Paltsyn, A. A. (2019) Neurotrophic brain factor – BDNF, Patogenez, 17, 83-88, doi: 10.25557/2310-0435.2019.03.83-88.

27. Hempstead, B. L. (2015) Brain-derived neurotrophic factor: three ligands, many actions, Trans. Am. Clin. Climatol. Assoc., 126, 9-19.

28. Giacobbo, L. B., Doorduin, J., Klein, H. C., Dierckx, R. A. J. O., Bromberg, E., and de Vries, E. F. J. (2019) Brain-derived neurotrophic factor in brain disorders: focus on neuroinflammation, Mol. Neurobiol., 56, 3295-3312, doi: 10.1007/s12035-018-1283-6.

29. Wang, M., Xie, Y., and Qin, D. (2021) Proteolytic cleavage of proBDNF to mBDNF in neuropsychiatric and neurodegenerative diseases, Brain Res. Bull., 166, 172-184, doi: 10.1016/j.brainresbull.2020.11.005.

30. Hill, R. A., Klug, M., Kiss Von Soly, S., Binder, M. D., Hannan, A. J., and van den Buuse, M. (2014) Sex-specific disruptions in spatial memory and anhedonia in a “two hit” rat model correspond with alterations in hippocampal brain-derived neurotrophic factor expression and signaling. Hippocampus, 24, 1197-1211, doi: 10.1002/hipo.22302.

31. Yeh, C. M., Huang, C. C., and Hsu, K. S. (2012) Prenatal stress alters hippocampal synaptic plasticity in young rat offspring through preventing the proteolytic conversion of pro-brain-derived neurotrophic factor (BDNF) to mature BDNF, J. Physiol., 590, 991-1010, doi: 10.1113/jphysiol.2011.222042.

32. Li, M., Du, W., Shao, F., and Wang, W. (2016) Cognitive dysfunction and epigenetic alterations of the BDNF gene are induced by social isolation during early adolescence, Behav. Brain Res., 313, 177-183, doi: 10.1016/j.bbr.2016.07.025.

33. Zubkov, E. A., Zorkina, Ya. A., Orshanskaya, E. V., Khlebnikova, N. N., Krupina, N. A., and Chekhnin, V. P. (2019) Post-weaning social isolation disturbs gene expression in rat brain structures, Bull. Exper. Biol. Med., 166, 364-368, doi: 10.1007/s10517-019-04351-0.

34. García-Horsman, J. A. (2020) The role of prolyl oligopeptidase, understanding the puzzle, Ann. Transl. Med., 8, 983, doi: 10.21037/atm-20-3412.

35. Männistö, P. T., and García-Horsman, J. A. (2017) Mechanism of action of prolyl oligopeptidase (PREP) in degenerative brain diseases: has peptidase activity only a modulatory role on the interactions of PREP with proteins? Front. Aging Neurosci., 9, 27, doi: 10.3389/fnagi.2017.00027.

36. Kushnareva, E. Yu., Krupina, N. A., Khlebnikova, N. N., Zolotov, N. N., and Kryzhanovskii, G. N. (2011) Activities of proline-specific peptidases in brain structures of rats with experimental anxiety-depressive state caused by administration dipeptidyl peptidase IV inhibitor in the early postnatal period, Bull. Exp. Biol. Med., 151, 675-679, doi: 10.1007/s10517-011-1413-x.

37. Khlebnikova, N. N., Krupina, N. A., Kushnareva, E. Yu., and Orlova, I. N. (2015) Differences in active avoidance conditioning in male and female rats with experimental anxiety-depressive disorder, Bull. Exp. Biol. Med., 159, 337-340, doi: 10.1007/s10517-015-2956-z.

38. Zubkov, E. A., Zorkina, Y. A., Orshanskaya, E. V., Khlebnikova, N. N., Krupina, N. A., and Chekhonin, V. P. (2017) Changes in gene expression profiles in adult rat brain after neonatal action of dipeptidyl peptidase-IV inhibitors, Neuropsychobiology, 76, 89-99, doi: 10.1159/000488367.

39. Nazarova, G. A., Zolotov, N. N., Krupina, N. A., Kraineva, V. A., Garibova, T. L., and Voronina, T. A. (2007) Changes in proline-specific peptidase activity in experimental model of retrograde amnesia, Eksperim. klinich. farmakol., 70, 6-8, doi: 10.30906/0869-2092-2007-70-6-6-8.

40. Krupina, N. A., Shirenova, S. D., and Khlebnikova, N. N. (2020) Prolonged social isolation, started early in life, impairs cognitive abilities in rats depending on sex, Brain Sci., 10, 799, doi: 10.3390/brainsci10110799.

41. Hall, F. S., Humby, T., Wilkinson, L., and Robbins, T. (1997) The effects of isolation-rearing of rats on behavioural responses to food and environmental novelty, Physiol. Behav., 62, 281-290, doi: 10.1016/S0031-9384(97)00115-7.

42. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem., 72, 248-254, doi: 10.1006/abio.1976.9999.

43. Benjamini, Y., and Hochberg, Y. (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing, J. R. Stat. Soc. Ser. B, 57, 289-300, doi: 10.1111/j.2517-6161.1995.tb02031.x.

44. Psychometrica: Computation of effect sizes. 11. Effect size calculator for non-parametric tests: Mann-Whitney-U, Wilcoxon-W and Kruskal-Wallis-H, URL: https://www.psychometrica.de/effect_size.html.

45. Cohen, J. (1988) Statistical Power Analysis for the Behavioral Sciences, Edn. 2, Hillsdale, Erlbaum.

46. Marco, E. M., Valero, M., de la Serna, O., Aisa, B., Borcel, E., et al. (2013) Maternal deprivation effects on brain plasticity and recognition memory in adolescent male and female rats, Neuropharmacology, 68, 223-231, doi: 10.1016/j.neuropharm.2012.08.014.

47. Teng, H. K., Teng, K. K., Lee, R., Wright, S., Tevar, S., et al. (2005) ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin, J. Neurosci., 25, 5455-5463, doi: 10.1523/JNEUROSCI.5123-04.2005.

48. Gibon, J., Buckley, S. M., Unsain, N., Kaartinen, V., Seguela, P., and Barker, P. A. (2015) proBDNF and p75NTR control excitability and persistent firing of cortical pyramidal neurons, J. Neurosci., 35, 9741-9753, doi: 10.1523/jneurosci.4655-14.2015.

49. Park, S.-S, Park, H. S., Kim, T. W., and Lee, S. J. (2020) Effects of swimming exercise on social isolation-induced memory impairment and apoptosis in old rats, J. Exerc. Rehabil., 16, 234-241, doi: 10.12965/jer.2040366.183.

50. Park, H.-S., Kim, T.-W., Park, S.-S., Lee, S.-J. (2020) Swimming exercise ameliorates mood disorder and memory impairment by enhancing neurogenesis, serotonin expression, and inhibiting apoptosis in social isolation rats during adolescence, J. Exerc. Rehabil., 16, 132-140, doi: 10.12965/jer.2040216.108.

51. Kim, T.-W., Park, S.-S., Shin, M.-S., Park, H.-S., and Baek, S.-S. (2020) Treadmill exercise ameliorates social isolation-induced memory impairment by enhancing silent information regulator-1 expression in rats, J. Exerc. Rehabil., 16, 227-233, doi: 10.12965/jer.2040400.200.

52. Carvalho-Netto, E. F., Myers, B., Jones, K., Solomon, M. B., and Herman, J. P. (2011) Sex differences in synaptic plasticity in stress-responsive brain regions following chronic variable stress, Physiol. Behav., 104, 242-247, doi: 10.1016/j.physbeh.2011.01.024.

53. Yau, S. Y., Li, A., Zhang, E. D., Christie, B. R., Xu, A., et al. (2014) Sustained running in rats administered corticosterone prevents the development of depressive behaviors and enhances hippocampal neurogenesis and synaptic plasticity without increasing neurotrophic factor levels, Cell Transplant., 23, 481-492, doi: 10.3727/096368914X678490.

54. Babkova, K., Korabecny, J., Soukup, O., Nepovimova, E., Jun, D., and Kuca, K. (2017) Prolyl oligopeptidase and its role in the organism: attention to the most promising and clinically relevant inhibitors, Future Med. Chem., 9, 1015-1038, doi: 10.4155/fmc-2017-0030.

55. Yavas, E., Gonzalez, S., and Fanselow, M. S. (2019) Interactions between the hippocampus, prefrontal cortex, and amygdala support complex learning and memory, F1000Res., 31, 8, doi: 10.12688/f1000research.19317.1.

56. Fiedorowicz, A., Figiel, I., Kamińska, B., Zaremba, M., Wilk, S., and Oderfeld-Nowak, B. (2001) Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure, Brain Res., 912, 116-127, doi: 10.1016/s0006-8993(01)02675-0.

57. Bär, J. W., Rahfeld, J.-U., Schulz, I., Gans, K., Ruiz-Carrillo, D., et al. (2006) Prolyl endopeptidase cleaves the apoptosis rescue peptide humanin and exhibits an unknown post-cysteine cleavage specificity, Adv. Exp. Med. Biol., 575, 103-108, doi: 10.1007/0-387-32824-6_11.

58. Zahm, D. S. (1987) Neurotensin-immunoreactive neurons in the ventral striatum of the adult rat: ventromedial caudate-putamen, nucleus accumbens and olfactory tubercle, Neurosci. Lett., 81, 41-47, doi: 10.1016/0304-3940(87)90337-5.

59. Liu, Q., Hazan, A., Grinman, E., and Angulo, J. A. (2017) Pharmacological activation of the neurotensin receptor 1 abrogates the methamphetamine-induced striatal apoptosis in the mouse brain, Brain Res., 1659, 148-155, doi: 10.1016/j.brainres.2017.01.029.

60. Jalkanen, A. J., Puttonen, K. A., Venäläinen, J. I., Sinervä, V., Mannila, A., et al. (2006) Beneficial effect of prolyl oligopeptidase inhibition on spatial memory in young but not in old scopolamine-treated rats, Basic Clin. Pharmacol. Toxicol., 100, 132-138, doi: 10.1111/j.1742-7843.2006.00021.x.

61. Peltonen, I., Myöhänen, T. T., and Männistö, P. T. (2012) Different interactions of prolyl oligopeptidase and neurotensin in dopaminergic function of the rat nigrostriatal and mesolimbic pathways, Neurochem. Res., 37, 2033-2041, doi: 10.1007/s11064-012-0825-y.

62. Devader, C., Béraud-Dufour, S., Coppola, T., and Mazella, J. (2013) The anti-apoptotic role of neurotensin, Cells, 2, 124-135, doi: 10.3390/cells2010124.

63. Nykjaer, A., and Willnow, T. E. (2012) Sortilin: a receptor to regulate neuronal viability and function, Trends Neurosci., 35, 261270, doi: 10.1016/j.tins.2012.01.003.