Early stress in maternal deprivation affects the expression of OX1R in the limbic system of the brain and contributes to the development of anxiety-depressive symptoms in rats
- Authors: Pyurveev S.S.1,2, Dedanishvili N.S.1, Sekste E.A.1, Lebedev A.A.1, Bychkov E.R.1, Shabanov P.D.1
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Affiliations:
- Institute of Experimental Medicine
- Saint Petersburg State Pediatric Medical University
- Issue: Vol 22, No 2 (2024)
- Pages: 153-162
- Section: Original study articles
- URL: https://journal-vniispk.ru/RCF/article/view/263140
- DOI: https://doi.org/10.17816/RCF622940
- ID: 263140
Cite item
Abstract
BACKGROUND: Depressive states are becoming an increasingly common mental disorder and a serious social problem that places a heavy economic burden on society. Increasing data from preclinical and clinical studies indicate that orexins (neuropeptides, also known as hypocretins) and their receptors are involved in the pathogenesis of depression. The orexinergic system regulates disrupted functions in depressive states, such as sleep, reward system, eating behavior, stress response, and monoaminergic regulation. However, the exact role of orexins in behavioral and neurophysiological disorders in depression is still unclear.
AIM: This study aimed to examine the effect of early postnatal stress on the expression of OX1R orexin in the limbic system and the development of anxiety-depressive symptoms in rats.
MATERIALS AND METHODS: Maternal deprivation was used as a model of early postnatal stress (postpartum days 2–12). The animals were divided into the control (n = 20) and maternal deprivation (n = 20) groups. On day 90 of life, the influence of early postnatal stress on the development of anxiety-depressive symptoms in adult rats was analyzed using a package of behavioral tests, namely, raised cruciform maze, forced swimming Porsolt test, and two-bottle test. After the experiments, the animals were killed by decapitation, the brain was extracted and placed in the cold, and brain structures (hypothalamus and amygdala) were isolated, immediately frozen in liquid nitrogen, and stored at a temperature of −80°C for polymerase chain reaction analysis.
RESULTS: In the “raised cruciform maze,” the maternal deprivation group spent less time in the open arms of the maze, and the time spent in the closed sleeves increased relative to the control, which can be assessed as an increase in anxiety levels. In the Porsolt test, the maternal deprivation group had increased immobilization time relative to the control group. In the two-bottle sucrose preference test, the maternal deprivation group demonstrated a decreased preference for sucrose solution, which indicates the development of anhedonia. In the hypothalamus, the mRNA expression level of OX1R significantly decreased in the experimental group compared with that in the control group. A twofold decrease in the mRNA expression level of OX1R was also observed in the amygdala of the experimental group compared with that of the control group.
CONCLUSIONS: Early stress caused by maternal deprivation resulted in a decrease in OX1R orexin expression in the hypothalamus and amygdala and contributed to the development of anxiety-depressive symptoms in rats.
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##article.viewOnOriginalSite##About the authors
Sarng S. Pyurveev
Institute of Experimental Medicine; Saint Petersburg State Pediatric Medical University
Author for correspondence.
Email: dr.purveev@gmail.com
ORCID iD: 0000-0002-4467-2269
SPIN-code: 5915-9767
Russian Federation, Saint Petersburg; Saint Petersburg
Nikolai S. Dedanishvili
Institute of Experimental Medicine
Email: votrenicolas@mail.ru
ORCID iD: 0000-0001-6231-445X
SPIN-code: 9472-0556
Russian Federation, Saint Petersburg
Edgar A. Sekste
Institute of Experimental Medicine
Email: sekste_edgar@mail.ru
SPIN-code: 3761-0525
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgAndrey A. Lebedev
Institute of Experimental Medicine
Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204
Dr. Sci. (Biology), Professor
Russian Federation, Saint PetersburgEugenii R. Bychkov
Institute of Experimental Medicine
Email: bychkov@mail.ru
SPIN-code: 9408-0799
MD, Cand. Sci. (Medicine)
Russian Federation, Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477
MD, Dr. Sci. (Medicine), Professor
Russian Federation, Saint PetersburgReferences
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