The effects of intracerebroventricularly applied ghrelin on thymocytes and thymic architecture in rats of different ages

Authors

  • Jovana S. Todorović Institute of Social Medicine, Faculty of Medicine, University of Belgrade
  • Zorica J. Terzić Šupić Institute of Social Medicine, Faculty of Medicine, University of Belgrade
  • Sanja D. Mazić Institute of Medical Physiology, Faculty of Medicine, University of Belgrade
  • Jelena M. Suzić Lazić Department of Cardiology, University Clinical Center “Dr Dragiša Mišović – Dedinje”, Faculty of Medicine, University of Belgrade
  • Dejan T. Žikić Institute of Biophysics, Faculty of Medicine, University of Belgrade
  • Dejan M. Nešić Institute of Medical Physiology, Faculty of Medicine, University of Belgrade http://orcid.org/0000-0002-7794-3520

Keywords:

ghrelin, thymus, intracerebroventricularly (ICV), lymphoid tissue, thymocytes

Abstract

Paper description:

  • The growth hormone secretagogue receptor R1a, the receptor for ghrelin, is expressed in immune cells.
  • The influence of intracerebroventricularly administered ghrelin (1 μg/day/rat for 5 days) to rats of different ages (peripubertal (5 weeks), young (2 months) and middle-aged (6 months; n=10 per group), on thymus mass and thymic architecture was examined.
  • Intracerebroventricular application of ghrelin postponed thymic atrophy: the average weights of the thymuses were significantly higher in the ghrelin groups; ghrelin positively influenced the number of thymocytes and thymic structure.
  • Our results point to a stimulatory effect of ghrelin on thymic size and function.


Abstract: Ghrelin positively influences the total number of thymocytes and size of the thymus in 14-, 20- and 24-month-old rats. We examined the effect of centrally-applied ghrelin on thymus weight and structure in Wistar rats of different ages. The study included 30 male Wistar rats of three age groups: peripubertal (5-week-old rats), young (2 months) and adult (6 months). The animals of each age group were divided into control and experimental groups that were administered intracerebroventricularly (ICV) 1 μg ghrelin/5 μL saline daily for five consecutive days. Following treatment, the thymuses were isolated, weighed and processed for stereological analysis by the point-counting method. The average weights of the thymuses were significantly higher in the ghrelin groups with respect to control rats (5 weeks: 444.90±18.03 vs 365.00±18.63; 2 months: 354.30±13.77 vs 257.00±9.60; 6 months: 365.00±15.90 vs 225.00±7.03, p<0.01). The absolute volume of lymphoid tissue was significantly higher in the ghrelin groups (5 weeks: 392.85±16.94 vs 294.48±33.37; 2 months: 309.30±12.10 vs 216.62±10.72; 6 months: 222.70±11.41 vs. 114.33±16.48, p<0.01). Ghrelin treatment restored thymic structure by increasing medullary cellularity, improving thymic medullary architecture and providing a clearer delineation between the cortex and medulla. This study shows the positive effects of centrally applied ghrelin on suppression of thymus atrophy, its weight and architecture.

https://doi.org/10.2298/ABS200416020T

Received: April 16, 2020; Revised: May 1, 2020; Accepted: May 3, 2020; Published online: May 11, 2020

How to cite this article: Todorović JS, Terzić Šupić ZJ, Mazić SD, Suzić Lazić JM, Žikić DD, Nešić DM. The effects of intracerebroventricularly applied ghrelin on thymocytes and thymic architecture in rats of different ages. Arch Biol Sci. 2020;72(2):265-70.

Downloads

Download data is not yet available.

References

Hale LP. Histologic and Molecular Assessment of Human Thymus. Ann Diagn Pathol. 2004;8(1):50-60.

Boehm T. Thymus development and function. Curr Opin Immunol. 2008;20:178-84.

Ventevogel MS, Sempowski GD. Thymic rejuvenation and aging. Curr Opin Immunol. 2013;25(4):516-22.

Rezzani R, Nardo L, Favero G, Peroni M, Rodella LF. Thymus and aging : morphological, radiological , and functional overview. Age (Omaha). 2014;36:313-51.

Muñoz JJ, García-Ceca J, Alfaro D, Stimamiglio MA, Cejalvo T, Jiménez E, Zapata AG. Organizing the thymus gland. Ann N Y Acad Sci. 2009;1153:14-9.

Zhang L, Sun L, Zhao Y. Thymic epithelial progenitor cells and thymus regeneration : an update. Cell Res. 2007;17:50-5.

Manley NR, Rothman Richie E, Blackburn CC, Condie BG, Sage J. Structure and function of the thymic microenvironment Nancy. Front Biosci. 2011;16:2461-77.

Jin R, Zhang J, Chen W. Thymic Output : Influence Factors and Molecular Mechanism. Cell Mol Immunol. 2006;3(5):341-50.

Holländer GA, Krenger W, Blazar BR. Emerging strategies to boost thymic function. Curr Opin Pharmacol. 2010;10(4):443-53.

Zdrojewicz Z, Pachura E, Pachura P. The Thymus: A Forgotten, But Very Important Organ. Adv Clin Exp Med. 2016;25(2):369-75.

Dominguez-Gerpe L, ReyMendez M. Evolution of the Thymus Size in Response to Physiological and Random Events Throughout Life. Microsc Res Tech. 2003;476:464-76.

Albarran-Zeckler RG, Sun Y, Smith RG. Physiological roles revealed by ghrelin and ghrelin receptor deficient mice. Peptides. 2011;32(11):2229-35.

Shanker A. Is thymus redundant after adulthood ? Immunol Lett. 2004;91:79-86.

Baatar D, Patel K, Taub DD. Molecular and Cellular Endocrinology The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol. 2011;340(1):44-58.

Savino W, Postel-vinay MC, Smaniotto S, Dardenne M. The Thymus Gland : a Target Organ for Growth Hormone. Scand J Immunol. 2002;55:442-52.

Okada Y, Sugita Y, Ohshima K, Morioka M, Komaki S, Miyoshi J, Abe H. Signaling of ghrelin and its functional receptor, the growth hormone secretagogue receptor, promote tumor growth in glioblastomas. Neuropathology. 2016;36(6):535-43.

Oztas B, Sahin D, Kir H, Eraldemir FC, Musul M, Kuskay S, Ates N. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1β, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model. Neuropeptides. 2017;61:31-7.

Dixit VD, Yang H, Sun Y, Weeraratna AT, Youm Y, Smith RG, Taub DD. Ghrelin promotes thymopoiesis during aging. J Clin Invest. 2007;117(10):2778-90.

Nesic DM, Stevanovic DM, Stankovic SD, Milosevic VL, Trajkovic V, Starcevic VP, Severs WB. Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats. Eur J Pharmacol. 2013;710(1-3):85-91.

Nešić D, Stevanović D, Đelić M, Mazić S, Trbojević-Stanković J, Soldatović I, Stajić-Trošić J, Starčević V. The effects of centrally applied ghrelin on appetite and metabolic parameters during aging. Dig J Nanomater Biostruct. 2014; 9(4):1439-49.

Radoman K, Živković V, Nikolić T, Stojić I, Raičević D, Jeremić J, Srejovic I, Jakovljevic V. Differences between α-linolenic and linoleic acid supplementation on the redox status and cardiodynamic parameters of male and female Wistar albino rats. Arch Biol Sci. 2018;70(2):223-31.

Aspinall R, Mitchell W. Reversal of age-associated thymic atrophy: Treatments, delivery, and side effects. Exp Gerontol. 2008;43:700-5.

Taub DD, Murphy WJ, Longo DL. Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways. Curr Opin Pharmacol. 2010;10(4):408-24.

Youm YH, Yang H, Sun Y, Smith RG, Manley NR, Vandanmagsar B, Dixit VD. Deficient ghrelin receptor-mediated signaling compromises thymic stromal cell microenvironment by accelerating thymic adiposity. J Biol Chem. 2009;284(11):7068-77.

Yin Y, Zhang W. The Role of Ghrelin in Senescence: A Mini-Review. Gerontology. 2016;62(2):155-62.

Downloads

Published

2020-07-01

How to Cite

1.
Todorović JS, Terzić Šupić ZJ, Mazić SD, Suzić Lazić JM, Žikić DT, Nešić DM. The effects of intracerebroventricularly applied ghrelin on thymocytes and thymic architecture in rats of different ages. Arch Biol Sci [Internet]. 2020Jul.1 [cited 2024Dec.22];72(2):265-70. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/5263

Issue

Vol. 72 No. 2 (2020)

Section

Articles

License

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.

Most read articles by the same author(s)