Early postnatal maternal temporary isolation stress in rats contributes to the development of anxiety-depressive symptoms in adulthood

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Abstract

BACKGROUND: Depressive disorders are becoming increasingly prevalent and represent a significant social issue with heavy economic implications.

AIM: To study the effects of maternal temporary isolation during early ontogenesis on the development of anxiety and depressive symptoms in adult rats.

MATERIALS AND METHODS: The study employed a maternal temporary isolation model as a form of early postnatal stress (from postnatal days 2 to 12). Two experimental groups were formed: a control group (n=20) and an “early maternal temporary isolation” group (n=20). On the 90th day of life, a behavioral test battery was used to assess the impact of early postnatal stress on the development of anxiety-depressive symptoms. The behavioral tests included the elevated plus maze, the Porsolt forced swim test, and the sucrose preference test.

RESULTS: Behavioral testing in the elevated plus maze revealed that rats exposed to early maternal temporary isolation showed reduced time spent in the open arms and increased time in the closed arms compared to the control group, indicating heightened anxiety levels. In the Porsolt test, the early isolation group demonstrated increased immobility time compared to the control group. In the sucrose preference test, the early isolation group exhibited reduced sucrose solution preference, indicative of anhedonia.

CONCLUSION: Stress exposure during early ontogenesis, a critical period for the development and maturation of brain structures responsible for psychoemotional behavior, can lead to their dysregulation and serves as a predictor for the development of anxiety-depressive symptoms in adult rats.

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About the authors

Sarng S. Pyurveev

Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

Author for correspondence.
Email: dr.purveev@gmail.com
ORCID iD: 0000-0002-4467-2269
SPIN-code: 5915-9767

MD, PhD, Assistant Professor, Department of Pathological Physiology with the Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation; Research Associate, Department of Neuropharmacology, Institute of Experimental Medicine

Russian Federation, Saint Petersburg; Saint Petersburg

Mikhail S. Nekrasov

Saint Petersburg State Pediatric Medical University

Email: nekrasov2013@inbox.ru
ORCID iD: 0000-0002-9434-1433
SPIN-code: 8704-2209

Postgraduate Student of the Department of Pharmacology with a Course of Clinical Pharmacology and Pharmacoeconomics

Russian Federation, Saint Petersburg

Andrei G. Vasiliev

Saint Petersburg State Pediatric Medical University

Email: avas7@mail.ru
ORCID iD: 0000-0002-8539-7128
SPIN-code: 1985-4025

MD, PhD, Dr. Sci. (Medicine), Professor, Head of the Department of Pathological Physiology with a Course in Immunology

Russian Federation, Saint Petersburg

Nikolai S. Dedanishvili

Saint Petersburg State Pediatric Medical University

Email: votrenicolas@mail.ru
ORCID iD: 0000-0001-6231-445X
SPIN-code: 9472-0556

6th year Student of the Pediatric Faculty

Russian Federation, Saint Petersburg

Nikita A. Luzhnov

Institute of Experimental Medicine; Samara State Medical University

Email: Nik.luzhnov.01@mail.ru
ORCID iD: 0009-0008-0628-4389

6th year Student of the Pediatric Faculty of Samara State Medical University, Ministry of Health of the Russian Federation; laboratory research assistant, Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine

Russian Federation, Saint Petersburg; Samara

Rodion V. Korablev

Saint Petersburg State Pediatric Medical University

Email: rodion.korablev@gmail.com
ORCID iD: 0009-0004-5754-8437
SPIN-code: 4969-6038

MD, PhD, Assistant Professor, Department of Pathological Physiology with the Course of Immunopathology

Russian Federation, Saint Petersburg

Anna V. Vasilieva

Saint Petersburg State Pediatric Medical University

Email: a-bondarenko@yandex.ru
ORCID iD: 0009-0008-2356-1552
SPIN-code: 5333-0144

MD, PhD, Assistant Professor, Department of Pathological Physiology with the Course of Immunopathology

Russian Federation, Saint Petersburg

Adelina M. Maksyuta

Saint Petersburg State Pediatric Medical University

Email: zheludkova.adelina@mail.ru
ORCID iD: 0000-0003-2043-8125

6th year Student of the Pediatric Faculty

Russian Federation, Saint Petersburg

Anastasia R. Avdeeva

Saint Petersburg State Pediatric Medical University

Email: anastas-avdeeva@mail.ru
ORCID iD: 0009-0004-3037-4545

6th year Student of the Pediatric Faculty

Russian Federation, Saint Petersburg

Tatiana E. Lebedeva

Saint Petersburg State Pediatric Medical University

Email: aalebedev-iem@rambler.ru
ORCID iD: 0009-0007-5494-6095

Assistant Professor, Department of General and Medical Chemistry named after Prof. V.V. Khorunzhey

Russian Federation, Saint Petersburg

Aleftina A. Kravtsova

Saint Petersburg State Pediatric Medical University

Email: aleftinakravcova@mail.ru
ORCID iD: 0000-0002-0657-3390
SPIN-code: 6762-1182

PhD, Associate Professor, Department of Pathological Physiology with the Course of Immunopathology

Russian Federation, Saint Petersburg

Anastasiya Yu. Bodrova

Institute of Experimental Medicine

Email: nastya.namanchuk.00@mail.ru
ORCID iD: 0009-0001-9107-9871

Research Laboratory Assistant, Department of Neuropharmacology named after S.V. Anichkov

Russian Federation, Saint Petersburg

Shuanet A. Ibragimova

Institute of Experimental Medicine

Email: Fatima.ibragimova.1981@mail.ru
ORCID iD: 0009-0003-3709-7993

Research Laboratory Assistant, Department of Neuropharmacology named after S.V. Anichkov

Russian Federation, Saint Petersburg

Andrei A. Lebedev

Saint Petersburg State Pediatric Medical University; Saint Petersburg University of Management Technologies and Economics

Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204

PhD, Dr. Sci. (Pharmacology), Professor, Head of the Laboratory of General Pharmacology, Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine

Russian Federation, Saint Petersburg; Saint Petersburg

References

  1. Balakina ME, Degtyareva EV, Nekrasov MS, et al. Effect of early postnatal stress upon psychoemotional state and development of excessive consumption of high-carbohydrate food in rats. Russian biomedical research. 2021;6(2):27–37. EDN: ABECPH
  2. Butkevich IP, Shimarayeva TN, Mikhaylenko VA. Prenatal effects of buspirone and stress on behavioral reactions in rat pups of different sexes during period of ontogeny with low level of brain serotonin. Pediatrician (St. Petersburg). 2014;5(1):90–96. doi: 10.17816/PED5190-96 EDN: SFWHDJ
  3. Bychkov ER, Karpova IV, Tsikunov SG, et al. The effect of acute mental stress on the exchange of monoamines in the mesocortical and nigrostriatal systems of the rat brain. Pediatrician (St. Petersburg). 2021;12(6):35–42. doi: 10.17816/PED12635-42 EDN: VFATQN
  4. Vasiliev AG, Komyakov BK, Tagirov NS, Musaev SA. Percutaneous nephrolithitripsy in the treatment of coral calculus nephrolithiasis. Bulletin of the Saint Petersburg State Medical Academy named after I.I. Mechnikov. 2009;(4):183–186. EDN: NRLWIX
  5. Vasiliev AG, Morozova KV, Brus TV, et al. The role of homocystein metabolic disorders in pathological processes. Russian biomedical research. 2022;7(1):44–59. doi: 10.56871/1453.2022.70.70.007 EDN: QEFGQF
  6. Dedanishvili NS, Degtyareva EV, Pomigalova AM. Analysis of different models of cognitive impairment in rats. Forcipe. 2022;5(S3):888–889. EDN: BDIGKJ (In Russ.)
  7. Dedanishvili NS, Pomigalova AM, Bezrukov DD, et al. Early life stress as a risk factor for chronic alcoholization. Methods of pharmacological correction. Forcipe. 2022;5(S3):810–811. EDN: XNZQOP (In Russ.)
  8. Isaev DN. Emotional stress. Psychosomatic and somatopsychic disorders in children. Saint Petersburg: Speech; 2005. 400 p. EDN: QLJVQB (In Russ.)
  9. Lebedev AA, Purveev SS, Sexte EA, et al. Studying the involvement of ghrelin in the mechanism of gambling addiction in rats after exposure to psychogenic stressors in early ontogenesis. Russian journal of physiology. 2023;109(8):1080–1093. doi: 10.31857/S086981392308006X EDN: FCMBCJ
  10. Lebedev AA, Pyurveev SS, Sekste EA, et al. Models of maternal neglect and social isolation in ontogenesis evince elements of gambling dependence in animals, increasing ghsr1a expression in cerebral structures. Journal of addiction problems. 2022;(11–12):44–66. EDN: SSLSSZ
  11. Pyurveev SS, Nekrasov MS, Dedanishvili NS, et al. Chronic mental stress in early ontogenesis increased risks of development for chemical and non-chemical forms of addiction. Reviews on Clinical Pharmacology and Drug Therapy. 2023;21(1):69–78. doi: 10.17816/RCF21169-78 EDN: GJBUYN
  12. Tagirov NS, Nazarov TH, Vasilev AG, et al. The experience of using percutaneous nephrolithotripsy and contact ureterolithotripsy in the complex treatment of urolithiasis. Preventive and clinical medicine. 2012;(4):30–33. EDN: PWKOLR
  13. Khaytsev NV, Vasiliev AG, Trashkov AP, et al. The influence of sex and age upon response of white rats to hypoxic hypoxia. Pediatrician (St. Petersburg). 2015;6(2):71–77. EDN: UGQSZJ
  14. Berg L, Rostila M, Hjern A. Parental death during childhood and depression in young adults — A national cohort study. J Child Psychol Psychiatry. 2016;57(9):1092–1098. doi: 10.1111/jcpp.12560
  15. Branchi I, Curley JP, D’Andrea I, et al. Early interactions with mother and peers independently build adult social skills and shape BDNF and oxytocin receptor brain levels. Psychoneuroendocrinology. 2013;38(4):522–532. doi: 10.1016/j.psyneuen.2012.07.010
  16. Brás JP, Guillot de Suduiraut I, Zanoletti O, et al. Stress-induced depressive-like behavior in male rats is associated with microglial activation and inflammation dysregulation in the hippocampus in adulthood. Brain Behav Immun. 2022;99:397–408. doi: 10.1016/j.bbi.2021.10.018
  17. Health Quality Ontario. Psychotherapy for major depressive disorder and generalized anxiety disorder: A health technology assessment. Ont Health Technol Assess Ser. 2017;17(15):1–167.
  18. Lee J, Chi S, Lee M-S. Molecular biomarkers for pediatric depressive disorders: A narrative review. Int J Mol Sci. 2021;22(18):10051. doi: 10.3390/ijms221810051
  19. Levine S, Huchton DM, Wiener SG, Rosenfeld P. Time course of the effect of maternal deprivation on the hypothalamic-pituitary-adrenal axis in the infant rat. Dev Psychobiol. 1991;24(8):547–558. doi: 10.1002/dev.420240803
  20. Li Z, Ruan M, Chen J, Fang Y. Major depressive disorder: advances in neuroscience research and translational applications. Neurosci Bull. 2021;37(6):863–880. doi: 10.1007/s12264-021-00638-3
  21. Loi M, Koricka S, Lucassen PJ, Joëls M. Age- and sex-dependent effects of early life stress on hippocampal neurogenesis. Front Endocrinol. 2014;5:13. doi: 10.3389/fendo.2014.00013
  22. Lorigooini Z, Boroujeni SN, Sayyadi-Shahraki M, et al. Limonene through attenuation of neuroinflammation and nitrite level exerts antidepressant-like effect on mouse model of maternal separation stress. Behav Neurol. 2021;1:8817309. doi: 10.1155/2021/8817309
  23. Norkeviciene A, Gocentiene R, Sestokaite A, et al. A systematic review of candidate genes for major depression. Medicina. 2022;58(2):285. doi: 10.3390/medicina58020285
  24. Pyurveev SS, Sizov VV, Lebedev AA, et al. Registration of changes in the level of extracellular dopamine in the nucleus accumbens by fast-scan cyclic voltammetry during stimulation of the zone of the ventral tegmentаl area, which also caused a self-stimulation. J Evol Biochem Physiol. 2022;58(5):1613–1622. doi: 10.1134/s0022093022050295
  25. Rentesi G, Antoniou K, Marselos M, et al. Early maternal deprivation-induced modifications in the neurobiological, neurochemical and behavioral profile of adult rats. Behav Brain Res. 2013;244:29–37. doi: 10.1016/j.bbr.2013.01.040
  26. Rosenfeld P, Suchecki D, Levine S. Multifactorial regulation of the hypothalamic-pituitary-adrenal axis during development. Neurosci Biobehav Rev. 1992;16(4):553–568. doi: 10.1016/S0149-7634(05)80196-4
  27. Song J, Kim Y-K. Animal models for the study of depressive disorder. CNS Neurosci Ther. 2021;27(6):633–642. doi: 10.1111/cns.13622
  28. Lebedev AA, Pyurveev SS, Sexte EA, et al. Studying the Involvement of ghrelin in the mechanism of gambling addiction in rats after exposure to psychogenic stressors in early ontogenesis. J Evol Biochem Physiol. 2023;59(4):1402–1413. doi: 10.1134/S1234567823040316
  29. Tofoli SMC, Von Werne Baes C, Martins CMS, Juruena M. Early life stress, HPA axis, and depression. Psychol Neurosci. 2011;4(2):229–234. doi: 10.3922/j.psns.2011.2.008
  30. Wang R, Wang W, Xu J, et al. Jmjd3 is involved in the susceptibility to depression induced by maternal separation via enhancing the neuroinflammation in the prefrontal cortex and hippocampus of male rats. Exp Neurol. 2020;328:113254. doi: 10.1016/j.expneurol.2020.113254

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Immobility time of animals in the Porsolt test after temporary isolation from the mother during early ontogeny. ***р <0.001, significant differences compared with the control group; immobility time is expressed in seconds; M±m.

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3. Fig. 2. Sucrose preference test. **р <0.01, significant differences compared to the control group; M±m.

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