https://doi.org/10.4081/ejh.2021.3287
Effect of unacylated ghrelin on peripheral nerve regeneration
Submitted: 7 June 2021
Accepted: 13 August 2021
Published: 4 November 2021
Accepted: 13 August 2021
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Ghrelin is a circulating peptide hormone released by enteroendocrine cells of the gastrointestinal tract as two forms, acylated and unacylated. Acylated ghrelin (AG) binds to the growth hormone secretagogue receptor 1a (GHSR1a), thus stimulating food intake, growth hormone release, and gastrointestinal motility. Conversely, unacylated GHR (UnAG), through binding to a yet unidentified receptor, protects the skeletal muscle from atrophy, stimulates muscle regeneration, and protects cardiomyocytes from ischemic damage. Recently, interest about ghrelin has raised also among neuroscientists because of its effect on the nervous system, especially the stimulation of neurogenesis in spinal cord, brain stem, and hippocampus. However, few information is still available about its effectiveness on peripheral nerve regeneration. To partially fill this gap, the aim of this study was to assess the effect of UnAG on peripheral nerve regeneration after median nerve crush injury and after nerve transection immediately repaired by means of an end-to-end suture. To this end, we exploited FVB1 Myh6/Ghrl transgenic mice in which overexpression of the ghrelin gene (Ghrl) results in selective up-regulation of circulating UnAG levels, but not of AG. Regeneration was assessed by both functional evaluation (grasping test) and morphometrical analysis of regenerated myelinated axons. Results obtained lead to conclude that UnAG could have a role in development of peripheral nerves and during more severe lesions.
Navarro X, Vivo M, Valero-Cabre A. Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 2007;82:163-201.
DOI: https://doi.org/10.1016/j.pneurobio.2007.06.005
Sun W, Sun C, Zhao H, Lin H, Han Q, Wang J, et al. Improvement of sciatic nerve regeneration using laminin-binding human NGF-beta. PLoS One 2009;4:e6180.
DOI: https://doi.org/10.1371/journal.pone.0006180
Caillaud M, Richard L, Vallat JM, Desmouliere A, Billet F. Peripheral nerve regeneration and intraneural revascularization. Neural Regen Res 2019;14:24-33.
DOI: https://doi.org/10.4103/1673-5374.243699
Muller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, et al. Ghrelin. Mol Metab 2015;4:437-60.
DOI: https://doi.org/10.1016/j.molmet.2015.03.005
Johansson I, Destefanis S, Aberg ND, Aberg MA, Blomgren K, Zhu C, et al. Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells. Endocrinology 2008;149:2191-9.
DOI: https://doi.org/10.1210/en.2007-0733
Kent BA, Beynon AL, Hornsby AK, Bekinschtein P, Bussey TJ, Davies JS, et al. The orexigenic hormone acyl-ghrelin increases adult hippocampal neurogenesis and enhances pattern separation. Psychoneuroendocrinology 2015;51:431-9.
DOI: https://doi.org/10.1016/j.psyneuen.2014.10.015
Moon M, Kim S, Hwang L, Park S. Ghrelin regulates hippocampal neurogenesis in adult mice. Endocr J 2009;56:525-31.
DOI: https://doi.org/10.1507/endocrj.K09E-089
Porporato PE, Filigheddu N, Reano S, Ferrara M, Angelino E, Gnocchi VF, et al. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. J Clin Invest 2013;123:611-22.
DOI: https://doi.org/10.1172/JCI39920
Guneli E, Onal A, Ates M, Bagriyanik HA, Resmi H, Orhan CE, et al. Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats. Neurosci Lett 2010;479:226-30.
DOI: https://doi.org/10.1016/j.neulet.2010.05.066
Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008;132:387-96.
DOI: https://doi.org/10.1016/j.cell.2008.01.017
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-60.
DOI: https://doi.org/10.1038/45230
Agosti E, De Feudis M, Angelino E, Belli R, Alves Teixeira M, Zaggia I, et al. Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice. Aging (Albany NY) 2020;12:13939-57.
DOI: https://doi.org/10.18632/aging.103802
Delhanty PJ, Sun Y, Visser JA, van Kerkwijk A, Huisman M, van Ijcken WF, et al. Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice. PLoS One 2010;5:e11749.
DOI: https://doi.org/10.1371/journal.pone.0011749
Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002;159:1029-37.
DOI: https://doi.org/10.1083/jcb.200207165
Granata R, Settanni F, Biancone L, Trovato L, Nano R, Bertuzzi F, et al. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology 2007;148:512-29.
DOI: https://doi.org/10.1210/en.2006-0266
Reano S, Angelino E, Ferrara M, Malacarne V, Sustova H, Sabry O, et al. Unacylated ghrelin enhances satellite cell function and relieves the dystrophic phenotype in Duchenne muscular dystrophy mdx model. Stem Cells 2017;35:1733-46.
DOI: https://doi.org/10.1002/stem.2632
Angelino E, Reano S, Bollo A, Ferrara M, De Feudis M, Sustova H, et al. Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal. Endocrine 2018;62:129-35.
DOI: https://doi.org/10.1007/s12020-018-1606-4
Ronchi G, Raimondo S, Varejao AS, Tos P, Perroteau I, Geuna S. Standardized crush injury of the mouse median nerve. J Neurosci Methods 2010;188:71-5.
DOI: https://doi.org/10.1016/j.jneumeth.2010.01.024
Raimondo S, Fornaro M, Di Scipio F, Ronchi G, Giacobini-Robecchi MG, Geuna S. Chapter 5: Methods and protocols in peripheral nerve regeneration experimental research: part II-morphological techniques. Int Rev Neurobiol 2009;87:81-103.
DOI: https://doi.org/10.1016/S0074-7742(09)87005-0
Geuna S. Appreciating the difference between design-based and model-based sampling strategies in quantitative morphology of the nervous system. J Comp Neurol 2000;427:333-9.
DOI: https://doi.org/10.1002/1096-9861(20001120)427:3<333::AID-CNE1>3.0.CO;2-T
Geuna S, Tos P, Battiston B, Guglielmone R. Verification of the two-dimensional disector, a method for the unbiased estimation of density and number of myelinated nerve fibers in peripheral nerves. Ann Anat 2000;182:23-34.
DOI: https://doi.org/10.1016/S0940-9602(00)80117-X
Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin--a hormone with multiple functions. Front Neuroendocrinol 2004;25:27-68.
DOI: https://doi.org/10.1016/j.yfrne.2004.03.002
Fields D, Miranpuri S, Miranpuri G, Resnick D. The multifunctional and multi-system influence of Ghrelin in the treatment of diabetic and spinal cord injury induced Neuropathy. Ann Neurosci 2011;18:118-22.
DOI: https://doi.org/10.5214/ans.0972.7531.1118309
Zhou CH, Li X, Zhu YZ, Huang H, Li J, Liu L, et al. Ghrelin alleviates neuropathic pain through GHSR-1a-mediated suppression of the p38 MAPK/NF-kappaB pathway in a rat chronic constriction injury model. Reg Anesth Pain Med 2014;39:137-48.
DOI: https://doi.org/10.1097/AAP.0000000000000050
Tsuchimochi W, Kyoraku I, Yamaguchi H, Toshinai K, Shiomi K, Kangawa K, et al. Ghrelin prevents the development of experimental diabetic neuropathy in rodents. Eur J Pharmacol 2013;702:187-93.
DOI: https://doi.org/10.1016/j.ejphar.2013.01.035
Ueno H, Shiiya T, Nagamine K, Tsuchimochi W, Sakoda H, Shiomi K, et al. Clinical application of ghrelin for diabetic peripheral neuropathy. Endocr J 2017;64:S53-7.
DOI: https://doi.org/10.1507/endocrj.64.S53
Hernandez-Cortes P, Toledo-Romero MA, Delgado M, Gonzalez-Rey E, Gomez Sanchez R, Prados-Olleta N, et al. Ghrelin and adipose-derived mesenchymal stromal cells improve nerve regeneration in a rat model of epsilon-caprolactone conduit reconstruction. Histol Histopatho. 2017;32:627-37.
Asakawa A, Inui A, Fujimiya M, Sakamaki R, Shinfuku N, Ueta Y, et al. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut 2005;54:18-24.
DOI: https://doi.org/10.1136/gut.2004.038737
Delhanty PJ, Neggers SJ, van der Lely AJ. Mechanisms in endocrinology: Ghrelin: the differences between acyl- and des-acyl ghrelin. Eur J Endocrinol 2012;167:601-8.
DOI: https://doi.org/10.1530/EJE-12-0456
How to Cite
Ronchi, G., Tos, P., Angelino, E., Muratori, L., Reano, S., Filigheddu, N., … Raimondo, S. (2021). Effect of unacylated ghrelin on peripheral nerve regeneration. European Journal of Histochemistry, 65(s1). https://doi.org/10.4081/ejh.2021.3287
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