Increased mRNA grelin receptor expression in rat cubs brain structures in models of separation from mother and social isolation
- Authors: Pyurveev S.S.1,2, Lebedev A.A.2, Sexte E.A.2, Bychkov E.R.2, Dedanishvili N.S.1, Tagirov N.S.1, Shabanov P.D.2
-
Affiliations:
- Saint Petersburg State Pediatric Medical University
- Institute of Experimental Medicine
- Issue: Vol 14, No 2 (2023)
- Pages: 49-58
- Section: Original studies
- URL: https://ogarev-online.ru/pediatr/article/view/131610
- DOI: https://doi.org/10.17816/PED14249-58
- ID: 131610
Cite item
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.
Keywords
Full Text
##article.viewOnOriginalSite##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 PetersburgAndrei 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 PetersburgEdgar 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 PetersburgEugenii 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 PetersburgNikolay S. Dedanishvili
Saint Petersburg State Pediatric Medical University
Email: votrenicolas@mail.ru
SPIN-code: 9472-0556
Student
Russian Federation, Saint PetersburgNair 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 PetersburgPetr 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 PetersburgReferences
- 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.)
- 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
- 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
- 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
- Shabanov PD, Lebedev AA, Meshcherov ShK. Dofamin i podkreplyayushchie sistemy mozga. Saint Petersburg: Lan’, 2002. 208 p. (In Russ.)
- Shabanov PD, Meshcherov ShK, Lebedev AA. Sindrom sotsial’noi izolyatsii. Saint Petersburg: Ehlbi-SPb, 2004. (In Russ.)
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Hedegaard MA, Holst B. The complex signaling pathways of the ghrelin receptor. Endocrinology. 2020;161(4): bqaa020. doi: 10.1210/endocr/bqaa020
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
