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Article

A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland

by
Vadim Tseilikman
1,
Maria Komelkova
1,2,3,
Marina V. Kondashevskaya
4,
Eugenia Manukhina
1,5,6,
H. Fred Downey
1,6,
Valerii Chereshnev
2,
Margarita Chereshneva
2,
Pavel Platkovskii
1,
Anna Goryacheva
5,
Anton Pashkov
1,
Julia Fedotova
7,8,
Olga Tseilikman
1,
Natalya Maltseva
1,
Olga Cherkasova
9,
Charlotte Steenblock
10,
Stefan R. Bornstein
10,11,
Barbara Ettrich
12,
George P. Chrousos
1,13 and
Enrico Ullmann
1,10,14,*
1
School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia
2
Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia
3
Faculty of Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
4
Laboratory for Immunomorphology of Inflammation, Research Institute of Human Morphology, 117418 Moscow, Russia
5
Laboratory for Regulatory Mechanisms of Stress and Adaptation, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
6
Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
7
Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology RAS, 6 Emb. Makarova, 199034 Saint Petersburg, Russia
8
International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, 191002 Saint Petersburg, Russia
9
Biophysics Laboratory, Institute of Laser Physics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
10
Department of Medicine, Technical University of Dresden, 01309 Dresden, Germany
11
Rayne Institute, Division of Diabetes & Nutritional Sciences, Endocrinology and Diabetes, Faculty of Life Sciences & Medicine, Kings College London, London SE5 9PJ, UK
12
Department of Psychiatry and Psychotherapy, University of Leipzig, 04107 Leipzig, Germany
13
University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
14
Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Leipzig, 04107 Leipzig, Germany
 
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*
Author to whom correspondence should be addressed.
Academic Editor: Paola Marcolongo
Int. J. Mol. Sci. 2021, 22(24), 13235; https://doi.org/10.3390/ijms222413235
Received: 19 October 2021 / Revised: 29 November 2021 / Accepted: 1 December 2021 / Published: 8 December 2021
(This article belongs to the Special Issue Glucocorticoids and Metabolic Disorders)
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Abstract

Background: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production. Methods: Rats were exposed to PSS for ten days. Thirty days later, the rats’ anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex. Results: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats. Conclusion: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder. View Full-Text
Keywords: CPTSD; glucocorticoids; adrenal gland; behavior CPTSD; glucocorticoids; adrenal gland; behavior
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MDPI and ACS Style

Tseilikman, V.; Komelkova, M.; Kondashevskaya, M.V.; Manukhina, E.; Downey, H.F.; Chereshnev, V.; Chereshneva, M.; Platkovskii, P.; Goryacheva, A.; Pashkov, A.; Fedotova, J.; Tseilikman, O.; Maltseva, N.; Cherkasova, O.; Steenblock, C.; Bornstein, S.R.; Ettrich, B.; Chrousos, G.P.; Ullmann, E. A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland. Int. J. Mol. Sci. 2021, 22, 13235. https://doi.org/10.3390/ijms222413235

AMA Style

Tseilikman V, Komelkova M, Kondashevskaya MV, Manukhina E, Downey HF, Chereshnev V, Chereshneva M, Platkovskii P, Goryacheva A, Pashkov A, Fedotova J, Tseilikman O, Maltseva N, Cherkasova O, Steenblock C, Bornstein SR, Ettrich B, Chrousos GP, Ullmann E. A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland. International Journal of Molecular Sciences. 2021; 22(24):13235. https://doi.org/10.3390/ijms222413235

Chicago/Turabian Style

Tseilikman, Vadim, Maria Komelkova, Marina V. Kondashevskaya, Eugenia Manukhina, H. F. Downey, Valerii Chereshnev, Margarita Chereshneva, Pavel Platkovskii, Anna Goryacheva, Anton Pashkov, Julia Fedotova, Olga Tseilikman, Natalya Maltseva, Olga Cherkasova, Charlotte Steenblock, Stefan R. Bornstein, Barbara Ettrich, George P. Chrousos, and Enrico Ullmann. 2021. "A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland" International Journal of Molecular Sciences 22, no. 24: 13235. https://doi.org/10.3390/ijms222413235

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