Increased mRNA grelin receptor expression in rat cubs brain structures in models of separation from mother and social isolation

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

BACKGROUND: Stress exposure at an early age can have serious long-term consequences for the development of the human body, leading to adaptive disorders, increased anxiety, depression and other mental disorders in people. The effect of stressors in the first weeks after birth affects the proliferation, differentiation and migration of neurons, in particular, the neurogenesis of hippocampal cells. Repetitive stress can lead to changes in the structure and function of the brain, including deterioration of memory and skill acquisition, reduced resistance to stress in the future, decreased immune system function and increased risk of depression and other mental illnesses.

AIM: The aim was to study the effect of social isolation weaning on the level of ghrelin receptor mRNA expression in the brain structures of Wistar rats.

MATERIALS AND METHODS: 60 male rats (8 litters) with a body weight of 230–250 g were used in the work and three experimental groups were formed: control (n = 20); “maternal deprivation” (n = 20); “social isolation” (n = 20). On the 90th day of life, the animals were decapitated, the brain was quickly extracted, placed in the cold and brain structures (hypothalamus, amygdala, prefrontal cortex) were isolated, immediately frozen in liquid nitrogen and stored at a temperature of –80°C until PCR analysis was performed. The data obtained were normalized to the expression level of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene and calculated in relative units with respect to the expression value of the GRLN-R gene for each structure separately by method 2 (-DeltaDelta C(T)).

RESULTS: In rats raised in conditions of social isolation, compared with the indicators of the control group and the group of animals with maternal deprivation (p < 0.05), an increase in the expression of the GHSR1A gene was noted in the hypothalamus. Whereas in rats after the stress of maternal deprivation in the amygdala there was an increase in the expression of the GHSR1A gene compared with the indicators in the control group of rats.

CONCLUSIONS: 1. In rats that survived weaning from the mother from the 2nd to the 12th postnatal day, a significant statistically significant increase in the expression of the GHSR1A gene was revealed in the hypothalamus in comparison with the control group and the social isolation group. 2. In rats raised in conditions of social isolation from their relatives, a significant statistically significant increase in the expression of the GHSR1A gene in the amygdala was revealed in comparison with the control group and the weaning group.

About the authors

Sarng S. Pyurveev

Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

Author for correspondence.
Email: dr.purveev@gmail.com
SPIN-code: 5915-9767

Assistant Professor, Department of Pathologic Physiology and Course Immunopathology; Junior Research Associate, Department of Neuropharmacology

Russian Federation, Saint Petersburg; Saint Petersburg

Andrei A. Lebedev

Institute of Experimental Medicine

Email: aalebedev-iem@rambler.ru
SPIN-code: 4998-5204

PhD, Dr. Biol. Sci. (Pharmacology), Head of the Laboratory of General Pharmacology, Department of Neuropharmacology

Russian Federation, Saint Petersburg

Edgar A. Sexte

Institute of Experimental Medicine

Email: dr.purveev@gmail.com
SPIN-code: 3761-0525

PhD, Senior Research Associate, Department of Neuropharmacology

Russian Federation, Saint Petersburg

Eugenii R. Bychkov

Institute of Experimental Medicine

Email: bychkov@mail.ru
SPIN-code: 9408-0799

MD, PhD (Pathophysiology), Head of the Laboratory of Chemistry and Pharmacology of Medicinal Compounds, Department of Neuropharmacology

Russian Federation, Saint Petersburg

Nikolay S. Dedanishvili

Saint Petersburg State Pediatric Medical University

Email: votrenicolas@mail.ru
SPIN-code: 9472-0556

Student

Russian Federation, Saint Petersburg

Nair S. Tagirov

Saint Petersburg State Pediatric Medical University

Email: ruslana73nair@mail.ru

MD, PhD, Dr. Sci. (Med.), Professor, Department of Pathologic Physiology and Course Immunopathology

Russian Federation, Saint Petersburg

Petr D. Shabanov

Institute of Experimental Medicine

Email: pdshabanov@mail.ru
SPIN-code: 8974-7477

MD, PhD, Dr. Sci. (Med.), Professor, Head of the Department of Neuropharmacology

Russian Federation, 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. (In Russ.)
  2. 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. (In Russ.) doi: 10.17816/PED12635-42
  3. Lebedev AA, Moskalev AR, Abrosimov ME, et al. Effect of neuropeptide Y antagonist BMS193885 on overeating and emotional responses induced by social isolation in rats. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(2):189–202. (In Russ.) doi: 10.17816/RCF192189-202
  4. Shabanov PD, Vinogradov PM, Lebedev AA, et al. Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):38–45. (In Russ.) doi: 10.17816/RCF15438-45
  5. Shabanov PD, Lebedev AA, Meshcherov ShK. Dofamin i podkreplyayushchie sistemy mozga. Saint Petersburg: Lan’, 2002. 208 p. (In Russ.)
  6. Shabanov PD, Meshcherov ShK, Lebedev AA. Sindrom sotsial’noi izolyatsii. Saint Petersburg: Ehlbi-SPb, 2004. (In Russ.)
  7. Börchers S, Krieger J-P, Maric I, et al. From an empty stomach to anxiolysis: molecular and behavioral assessment of sex differences in the ghrelin axis of rats. Front Endocrinol. 2022;13:901669. doi: 10.3389/fendo.2022.901669
  8. Cabral A, Portiansky E, Sanchez-Jaramillo E, et al. Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus. Psychoneuroendocrinology. 2016;67:27–39. doi: 10.1016/j.psyneuen.2016.01.027
  9. Catani C, Jacob N, Schauer E, et al. Family violence, war, and natural disasters: A study of the effect of extreme stress on children’s mental health in Sri Lanka. BMC Psychiatry. 2008;8:33. doi: 10.1186/1471-244X-8-33
  10. Deschaine SL, Leggio L. From “Hunger hormone” to “It’s complicated”: Ghrelin beyond feeding control. Physiology (Bethesda, Md.). 2022;37(1):5–15. doi: 10.1152/physiol.00024.2021
  11. Deschaine SL, Farokhnia M, Gregory-Flores A, et al. A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data. Addict Biol. 2022;27(1):e13033. doi: 10.1111/adb.13033
  12. Dos-Santos RC, Grover HM, Reis LC, et al. Electrophysiological effects of ghrelin in the hypothalamic paraventricular nucleus neurons. Front Cell Neurosci. 2018;12:275. doi: 10.3389/fncel.2018.00275
  13. Edwards A, Abizaid A. Driving the need to feed: insight into the collaborative interaction between ghrelin and endocannabinoid systems in modulating brain reward systems. Neurosci Biobehav Rev. 2016;66:33–53. doi: 10.1016/j.neubiorev.2016.03.032
  14. Fenoglio KA, Brunson KL, Baram TZ. Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects. Front Neuroendocrinol. 2006;27(2): 180–192. doi: 10.1016/j.yfrne.2006.02.001
  15. Hedegaard MA, Holst B. The complex signaling pathways of the ghrelin receptor. Endocrinology. 2020;161(4): bqaa020. doi: 10.1210/endocr/bqaa020
  16. Jensen M, Ratner C, Rudenko O, et al. Anxiolytic-like effects of increased ghrelin receptor signaling in the amygdala. Int J Neuropsychopharmacol. 2016;19(5): pyv123. doi: 10.1093/ijnp/pyv123
  17. Lang AJ, Aarons GA, Gearity J, et al. Direct and indirect links between childhood maltreatment, posttraumatic stress disorder, and women’s health. Behav Med. 2008;33(4):125–136. doi: 10.3200/BMED.33.4.125-136
  18. Navarro G, Rea W, Quiroz C, et al. Complexes of ghrelin GHS-R1a, GHS-R1b, and dopamine D1 receptors localized in the ventral tegmental area as main mediators of the dopaminergic effects of ghrelin. J Neurosci. 2022;42(6):940–953. doi: 10.1523/JNEUROSCI.1151-21.2021
  19. Ou-Yang B, Hu Y, Fei X-Y, et al. A meta-analytic study of the effects of early maternal separation on cognitive flexibility in rodent offspring. Dev Cogn Neurosci. 2022;56:101126. doi: 10.1016/j.dcn.2022.101126
  20. Panchenko AV, Popovich IG, Egormin PA, et al. Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice. Biogerontology. 2016;17(2):317–324. doi: 10.1007/s10522-015-9611-y
  21. Pina MM, Cunningham CL. Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit. Neurobiol Learn Mem. 2017;137:83–91. doi: 10.1016/j.nlm.2016.11.013
  22. 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 Phys. 2022;58:1613–1622. doi: 10.1134/S0022093022050295
  23. Roik RO, Lebedev AA, Shabanov PD. The value of extended amygdala structures in emotive effects of narcogenic with diverse chemical structure. Research Results in Pharmacology. 2019;5(3):11–19. doi: 10.3897/rrpharmacology.5.38389
  24. Sekste EA, Lebedev AA, Bychkov ER, et al. Increase in the level of orexin receptor 1 (OX1R) mRNA in the brain structures of rats prone to impulsivity in behavior. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry. 2022;16(1):38–44. doi: 10.1134/S1990750822010085
  25. Spencer SJ, Emmerzaal TL, Kozicz T, Andrews ZB. Ghrelin’s role in the hypothalamic-pituitary-adrenal axis stress response: implications for mood disorders. Biol Psychiatry. 2015;78(1):19–27. doi: 10.1016/j.biopsych.2014.10.021
  26. Stevanovic D, Milosevic V, Starcevic VP, Severs WB. The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats. Life Sci. 2007;80(9):867–872. doi: 10.1016/j.lfs.2006.11.018
  27. Sustkova-Fiserova M, Charalambous C, Khryakova A, et al. The role of ghrelin/GHS-R1A signaling in nonalcohol drug addictions. Int J Mol Sci. 2022;23(2):761. doi: 10.3390/ijms23020761
  28. Tsygan NV, Trashkov AP, Litvinenko IV, et al. Autoimmunity in acute ischemic stroke and the role of blood-brain barrier: the dark side or the light one? Front Med. 2019;13(4):420–426. doi: 10.1007/s11684-019-0688-6
  29. Zoicas I, Neumann ID. Maternal separation facilitates extinction of social fear in adult male mice. Behav Brain Res. 2016;297:323–328. doi: 10.1016/j.bbr.2015.10.034

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. 3-hour deprivation session: а — baby rats in individual plastic cups on the 3rd postnatal day; b — baby rats in individual plastic cups on the 10th postnatal day

Download (212KB)
3. Fig. 2. The level of GHSR1A mRNA in the hypothalamus of the rat brain. *p < 0.05 in relation to the control group; #p < 0.05 in relation to the maternal deprivation group. Control — a group of intact animals; MD — a group of weaning from the mother; CI — a group of social isolation

Download (133KB)
4. Fig. 3. The level of GHSR1A mRNA in the amygdala (а) and prefrontal cortex (b) of the rat brain. *p < 0.05 relative to the control group. Control — a group of intact animals; MD — a group of weaning from the mother; CI — a group of social isolation

Download (140KB)

Copyright (c) 2023 Eco-Vector


 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».