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

ORIGINAL STUDIES

Keywords:
early postnatal stress maternal temporary isolation during early ontogenesis anxiety depression ранний постнатальный стресс временная изоляция от матери в раннем онтогенезе тревожность депрессия

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.

Author Biographies

Sarng S. Pyurveev, Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

MD, Ph D, Assistant Professor, Department of Pathological Physiology with the Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation; address: 2 Litovskaya st.,
Saint Petersburg, 194100, Russia; Research Associate, Department of Neuropharmacology, Institute of Experimental Medicine, Saint Petersburg, Russia

Shuanet A. Ibragimova, Institute of Experimental Medicine

Research Laboratory Assistant,
Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine, Saint Petersburg, Russia

Anastasiya Yu. Bodrova, Institute of Experimental Medicine

Research Laboratory Assistant, Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine, Saint Petersburg, Russia

 

 

Aleftina A. Kravtsova, Saint Petersburg State Pediatric Medical University

Ph D, Associate Professor, Department of Pathological Physiology with the Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia

 

Tatiana E. Lebedeva, Saint Petersburg State Pediatric Medical University

Assistant Professor, Department of General and Medical Chemistry named after Prof. V.V. Khorunzhey, Saint Petersburg State Pediatric Medical University, Ministry of Health
of the Russian Federation, Saint Petersburg, Russia

 

Anastasia R. Avdeeva, Saint Petersburg State Pediatric Medical University

6th year Student of the Pediatric
Faculty, Saint Petersburg State Pediatric
Medical University, Ministry of Health
of the Russian Federation,
Saint Petersburg, Russia

Adelina M. Maksyuta, Saint Petersburg State Pediatric Medical University

 6th year Student of the Pediatric Faculty, Saint Petersburg State Pediatric Medical University,
Ministry of Health of the Russian Federation,
Saint Petersburg, Russia

 

Anna V. Vasilieva, Saint Petersburg State Pediatric Medical University

MD, Ph D, Assistant Professor,
Department of Pathological Physiology with the Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia

Rodion V. Korablev, Saint Petersburg State Pediatric Medical University

 MD, Ph D, Assistant Professor,
Department of Pathological Physiology with the Course of Immunopathology, Saint Petersburg State Pediatric University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia

Nikita A. Luzhnov, Institute of Experimental Medicine; Samara State Medical University

 

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

Nikolai S. Dedanishvili, Saint Petersburg State Pediatric Medical University

6th year Student of the Pediatric Faculty, Saint Petersburg State Pediatric University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia

Andrei G. Vasiliev, Saint Petersburg State Pediatric Medical University

MD, Ph D, Dr. Sci. (Medicine), Professor, Head of the Department of Pathological Physiology with a Course in Immunology, Saint Petersburg State Pediatric University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia

Mikhail S. Nekrasov, Saint Petersburg State Pediatric Medical University

Postgraduate Student of the Department of Pharmacology with a Course of Clinical Pharmacology and Pharmacoeconomics, Saint Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia

Andrei A. Lebedev, Institute of Experimental Medicine; Saint Petersburg University of Management Technologies and Economics

Ph D, Dr. Sci. (Pharmacology), Professor, Head of the Laboratory of General Pharmacology, Department of Neuropharmacology, Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine,
Saint Petersburg, Russia

 

References

Балакина М.Е., Дегтярева Е.В., Некрасов М.С., и др. Воздействие раннего постнатального стресса на психоэмоциональное состояние и развитие склонности к чрезмерному употреблению высокоуглеводной пищи у крыс // Российские биомедицинские исследования. 2021. Т. 6, № 2. С. 27–37. EDN: ABECPH.

Буткевич И.П., Шимараева Т.Н., Михайленко В.А. Пренатальные влияния буспирона и стресса на поведенческие реакции у разнополых крысят в период онтогенеза с пониженным уровнем мозгового серотонина // Педиатр. 2014. Т. 5, № 1. С. 90–96. doi: 10.17816/PED5190-96 EDN: SFWHDJ.

Бычков Е.Р., Карпова И.В., Цикунов С.Г., и др. Действие острого психического стресса на обмен моноаминов в мезокортикальной и нигростриатной системах головного мозга крыс // Педиатр. 2021. Т. 12, № 6. С. 35–42. doi: 10.17816/PED12635-42 EDN: VFATQN.

Васильев А.Г., Комяков Б.К., Тагиров Н.С., Мусаев С.А. Чрескожная нефролитотрипсия в лечении коралловидного нефролитиаза // Вестник Санкт-Петербургской государственной медицинской академии им. И.И. Мечникова. 2009. № 4. С. 183–186. EDN: NRLWIX.

Васильев А.Г., Морозова К.В., Брус Т.В., и др. Роль нарушений обмена гомоцистеина в патологических процессах // Российские биомедицинские исследования. 2022. Т. 7, № 1. С. 44–59. doi: 10.56871/1453.2022.70.70.007 EDN: QEFGQF.

Деданишвили Н.С., Дегтярева Е.В., Помигалова А.М. Анализ различных моделей когнитивных нарушений у крыс // Forcipe. 2022. Т. 5, № S3. С. 888–889. EDN: BDIGKJ.

Деданишвили Н.С., Помигалова А.М., Безруков Д.Д., и др. Стресс раннего возраста как фактор риска хронической алкоголизации. Методы фармакологической коррекции // Forcipe. 2022. Т. 5, № S3. С. 810–811. EDN: XNZQOP.

Исаев Д.Н. Эмоциональный стресс. Психосоматические и соматопсихические расстройства у детей. Санкт-Петербург: Речь, 2005. 400 с. EDN: QLJVQB.

Лебедев А.А., Пюрвеев С.С., Сексте Э.А., и др. Исследование участия грелина в механизмах игровой зависимости у крыс после воздействия психогенных стрессоров в раннем онтогенезе // Российский физиологический журнал им. И.М. Сеченова. 2023. Т. 109, № 8. С. 1080–1093. doi: 10.31857/S086981392308006X EDN: FCMBCJ.

Лебедев А.А., Пюрвеев С.С., Сексте Э.А., и др. Модели материнского пренебрежения и социальной изоляции в онтогенезе проявляют у животных элементы игровой зависимости, повышая экспрессию GHSR1A в структурах мозга // Вопросы наркологии. 2022. № 11–12. С. 44–66. EDN: SSLSSZ.

Пюрвеев С.С., Некрасов М.С., Деданишвили Н.С., и др. Действие хронического психического стресса в раннем онтогенезе повышает риски развития химической и нехимической форм зависимости // Обзоры по клинической фармакологии и лекарственной терапии. 2023. Т. 21, № 1. С. 69–78. doi: 10.17816/RCF21169-78 EDN: GJBUYN.

Тагиров Н.С., Назаров Т.Х., Васильев А.Г., и др. Опыт применения чрескожной нефролитотрипсии и контактной уретеролитотрипсии в комплексном лечении мочекаменной болезни // Профилактическая и клиническая медицина. 2012. № 4. С. 30–33. EDN: PWKOLR.

Хайцев Н.В., Васильев А.Г., Трашков А.П., и др. Влияние возраста и пола на характер ответных реакций белых крыс при действии хронической гипоксической гипоксии // Педиатр. 2015. Т. 6, № 2. С. 71–77. EDN: UGQSZJ.

Berg L., Rostila M., Hjern A. Parental death during childhood and depression in young adults — A national cohort study // J Child Psychol Psychiatry. 2016. Vol. 57, N9. P. 1092–1098. doi: 10.1111/jcpp.12560.

Branchi I., Curley J.P., 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. Vol. 38, N 4. P. 522–532. doi: 10.1016/j.psyneuen.2012.07.010.

Brás J.P., 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. Vol. 99. P. 397–408. doi: 10.1016/j.bbi.2021.10.018.

Health Quality Ontario. Psychotherapy for major depressive disorder and generalized anxiety disorder: A health technology assessment // Ont Health Technol Assess Ser. 2017. Vol. 17, N 15. P. 1–167.

Lee J., Chi S., Lee M.-S. Molecular biomarkers for pediatric depressive disorders: A narrative review // Int J Mol Sci. 2021. Vol. 22, N 18. ID 10051. doi: 10.3390/ijms221810051.

Levine S., Huchton D.M., Wiener S.G., Rosenfeld P. Time course of the effect of maternal deprivation on the hypothalamic-pituitary-adrenal axis in the infant rat // Dev Psychobiol. 1991. Vol. 24, N 8. P. 547–558. doi: 10.1002/dev.420240803.

Li Z., Ruan M., Chen J., Fang Y. Major depressive disorder: advances in neuroscience research and translational applications // Neurosci Bull. 2021. Vol. 37, N 6. P. 863–880. doi: 10.1007/s12264-021-00638-3.

Loi M., Koricka S., Lucassen P.J., Joëls M. Age- and sex-dependent effects of early life stress on hippocampal neurogenesis // Front Endocrinol. 2014. Vol. 5. ID 13. doi: 10.3389/fendo.2014.00013.

Lorigooini Z., Boroujeni S.N., 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. Vol. 1. ID 8817309. doi: 10.1155/2021/8817309.

Norkeviciene A., Gocentiene R., Sestokaite A., et al. A systematic review of candidate genes for major depression // Medicina. 2022. Vol. 58, N 2. ID 285. doi: 10.3390/medicina58020285.

Pyurveev S.S., Sizov V.V., Lebedev A.A., 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 tegment а l area, which also caused a self-stimulation // J Evol Biochem Physiol. 2022. Vol. 58, N 5. P. 1613–1622. doi: 10.1134/s0022093022050295.

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. Vol. 244. P. 29–37. doi: 10.1016/j.bbr.2013.01.040.

Rosenfeld P., Suchecki D., Levine S. Multifactorial regulation of the hypothalamic-pituitary-adrenal axis during development // Neurosci Biobehav Rev. 1992. Vol. 16, N 4. P. 553–568. doi: 10.1016/S0149-7634(05)80196-4.

Song J., Kim Y.-K. Animal models for the study of depressive disorder // CNS Neurosci Ther. 2021. Vol. 27, N 6. P. 633–642. doi: 10.1111/cns.13622.

Lebedev A.A., Pyurveev S.S., Sexte E.A., 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. Vol. 59, N 4. P. 1402–1413. doi: 10.1134/S1234567823040316.

Tofoli S.M.C., Von Werne Baes C., Martins C.M.S., Juruena M. Early life stress, HPA axis, and depression // Psychol Neurosci. 2011. Vol. 4, N 2. P. 229–234. doi: 10.3922/j.psns.2011.2.008.

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. Vol. 328. ID 113254. doi: 10.1016/j.expneurol.2020.113254.