https://doi.org/10.4081/ejh.2021.3310
Distribution of alpha-synuclein in normal human jejunum and its relations with the chemosensory and neuroendocrine system
Submitted: 30 July 2021
Accepted: 8 September 2021
Published: 2 November 2021
Accepted: 8 September 2021
Abstract Views: 1631
PDF: 838
HTML: 46
HTML: 46
Publisher's note
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.
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
Alpha-synuclein (α-syn) is a presynaptic neuronal protein and its structural alterations play an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). It has been originally described in the brain and aggregated α-syn has also been found in the peripheral nerves including the enteric nervous system (ENS) of PD patients. ENS is a network of neurons and glia found in the gut wall which controls gastrointestinal function independently from the central nervous system. Moreover, two types of epithelial cells are crucial in the creation of an interface between the lumen and the ENS: they are the tuft cells and the enteroendocrine cells (EECs). In addition, the abundant enteric glial cells (EGCs) in the intestinal mucosa play a key role in controlling the intestinal epithelial barrier. Our aim was to localize and characterize the presence of α-syn in the normal human jejunal wall. Surgical specimens of proximal jejunum were collected from patients submitted to pancreaticoduodenectomy and intestinal sections underwent immunohistochemical procedure. Alpha-syn has been found both at the level of ENS and the epithelial cells. To characterize α-syn immunoreactive epithelial cells, we used markers such as choline acetyltransferase (ChAT), useful for the identification of tuft cells. Then we evaluated the co-presence of α-syn with serotonin (5-HT), expressed in EECs. Finally, we used the low-affinity nerve growth factor receptor (p75NTR), to detect peripheral EGCs. The presence of α-syn has been demonstrated in EECs, but not in the tuft cells. Additionally, p75NTR has been highlighted in EECs of the mucosal layer and co-localized with α-syn in EECs but not with ChAT-positive cells. These findings suggest that α-syn could play a possible role in synaptic transmission of the ENS and may contribute to maintain the integrity of the epithelial barrier of the small intestine through EECs.
Carlson SS, Kelly RB. An antiserum specific for cholinergic synaptic vesicles from electric organ. J Cell Biol 1980;87:98-103.
Maroteaux L, Campanelli JT, Scheller RH. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 1988;8:2804-15.
Larsen KE, Schmitz Y, Troyer MD, Mosharov E, Dietrich P, Quazi AZ, et al. Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci 2006;26:11915-22.
Gitler AD, Shorter J. Prime time for alpha-synuclein. J Neurosci 2007;27:2433-4.
Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Sudhof TC. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 2010;329:1663-7.
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997;388:839-40.
Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA, et al. Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci 2006;26:41-50.
Al-Chalabi A, Durr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, et al. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS One 2009;4:e7114.
Scholz SW, Houlden H, Schulte C, Sharma M, Li A, Berg D, et al. SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol 2009;65:610-4.
Jellinger KA. Interaction between pathogenic proteins in neurodegenerative disorders. J Cell Mol Med 2012;16:1166-83.
Adamkov M, Plank L. [Prognostic relevance of histopathologic subtyping of nodular-sclerotic types of Hodgkin's disease].[Article in Slovak]. Bratisl Med J 1990;91:433-6.
Arima K, Ueda K, Sunohara N, Hirai S, Izumiyama Y, Tonozuka-Uehara H, et al. Immunoelectron-microscopic demonstration of NACP/alpha-synuclein-epitopes on the filamentous component of Lewy bodies in Parkinson's disease and in dementia with Lewy bodies. Brain Res 1998;808:93-100.
Galvin JE, Uryu K, Lee VM, Trojanowski JQ. Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. Proc Natl Acad Sci USA 1999;96:13450-5.
Chua CE, Tang BL. alpha-synuclein and Parkinson's disease: the first roadblock. J Cell Mol Med 2006;10:837-46.
Lema I, Araujo JR, Rolhion N, Demignot S. Jejunum: The understudied meeting place of dietary lipids and the microbiota. Biochimie 2020;178:124-36.
Walsh KT, Zemper AE. The enteric nervous system for epithelial researchers: Basic anatomy, techniques, and interactions with the epithelium. Cell Mol Gastroenterol Hepatol 2019;8:369-78.
Morroni M, Cangiotti AM, Cinti S. Brush cells in the human duodenojejunal junction: an ultrastructural study. J Anat 2007;211:125-31.
Chandra R, Hiniker A, Kuo YM, Nussbaum RL, Liddle RA. alpha-synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight 2017;2:e92295.
Sato A. Tuft cells. Anat Sci Int 2007;82:187-99.
Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, et al. Nerve Growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling. Cancer Cell 2017;31:21-34.
von Moltke J, Ji M, Liang HE, Locksley RM. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 2016;529:221-5.
Sbarbati A, Bramanti P, Benati D, Merigo F. The diffuse chemosensory system: exploring the iceberg toward the definition of functional roles. Prog Neurobiol 2010;91:77-89.
Sbarbati A, Crescimanno C, Benati D, Osculati F. Solitary chemosensory cells in the developing chemoreceptorial epithelium of the vallate papilla. J Neurocytol 1998;27:631-5.
Sbarbati A, Osculati F. The taste cell-related diffuse chemosensory system. Prog Neurobiol 2005;75:295-307.
Veronese S, Merigo F, Sbarbati A. Did we forget the diffuse chemosensory system when studying COVID-19? Immunol Lett 2021;231:26-7.
Bohorquez DV, Shahid RA, Erdmann A, Kreger AM, Wang Y, Calakos N, et al. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest 2015;125:782-6.
Ronnestad I, Akiba Y, Kaji I, Kaunitz JD. Duodenal luminal nutrient sensing. Curr Opin Pharmacol 2014;19:67-75.
Akiba Y, Hashimoto S, Kaunitz JD. Duodenal chemosensory system: enterocytes, enteroendocrine cells, and tuft cells. Curr Opin Gastroenterol 2020;36:501-8.
Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Bjorklund T, et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol 2014;128:805-20.
Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 2006;396:67-72.
Wakabayashi K, Mori F, Tanji K, Orimo S, Takahashi H. Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain. Acta Neuropathol 2010;120:1-12.
Kelly LP, Carvey PM, Keshavarzian A, Shannon KM, Shaikh M, Bakay RA, et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease. Mov Disord 2014;29:999-1009.
den HJW, Bethlem J. The distribution of Lewy bodies in the central and autonomic nervous systems in idiopathic paralysis agitans. J Neurol Neurosurg Psychiatry 1960;23:283-90.
Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F. Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses. Acta Neuropathol 1988;76:217-21.
Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 2010;119:689-702.
Devos D, Lebouvier T, Lardeux B, Biraud M, Rouaud T, Pouclet H, et al. Colonic inflammation in Parkinson's disease. Neurobiol Dis 2013;50:42-8.
Pouclet H, Lebouvier T, Coron E, Rouaud T, Flamant M, Toulgoat F, et al. Analysis of colonic alpha-synuclein pathology in multiple system atrophy. Parkinsonism Relat Disord 2012;18:893-5.
Sailaja BS, He XC, Li L. The regulatory niche of intestinal stem cells. J Physiol 2016;594:4827-36.
Schutz B, Ruppert AL, Strobel O, Lazarus M, Urade Y, Buchler MW, et al. Distribution pattern and molecular signature of cholinergic tuft cells in human gastro-intestinal and pancreatic-biliary tract. Sci Rep 2019;9:17466.
Stanzel RD, Lourenssen S, Blennerhassett MG. Inflammation causes expression of NGF in epithelial cells of the rat colon. Exp Neurol 2008;211:203-13.
Del Colle A, Israelyan N, Gross Margolis K. Novel aspects of enteric serotonergic signaling in health and brain-gut disease. Am J Physiol Gastrointest Liver Physiol 2020;318:G130-43.
Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S, et al. TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci USA 2009;106:3408-13.
Reynaud Y, Fakhry J, Fothergill L, Callaghan B, Ringuet M, Hunne B, et al. The chemical coding of 5-hydroxytryptamine containing enteroendocrine cells in the mouse gastrointestinal tract. Cell Tissue Res 2016;364:489-97.
Diwakarla S, Fothergill LJ, Fakhry J, Callaghan B, Furness JB. Heterogeneity of enterochromaffin cells within the gastrointestinal tract. Neurogastroenterol Motil 2017;29:e13101.
Koo A, Fothergill LJ, Kuramoto H, Furness JB. 5-HT containing enteroendocrine cells characterised by morphologies, patterns of hormone co-expression, and relationships with nerve fibres in the mouse gastrointestinal tract. Histochem Cell Biol 2021;155:623-36.
Bohorquez DV, Samsa LA, Roholt A, Medicetty S, Chandra R, Liddle RA. An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy. PLoS One 2014;9:e89881.
Resnikoff H, Metzger JM, Lopez M, Bondarenko V, Mejia A, Simmons HA, et al. Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates. J Inflamm Res 2019;12:113-26.
Schneider C, O'Leary CE, Locksley RM. Regulation of immune responses by tuft cells. Nat Rev Immunol 2019;19:584-93.
Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2005;2:416-22.
Clairembault T, Leclair-Visonneau L, Neunlist M, Derkinderen P. Enteric glial cells: new players in Parkinson's disease? Mov Disord 2015;30:494-8.
Yu YB, Li YQ. Enteric glial cells and their role in the intestinal epithelial barrier. World J Gastroenterol 2014;20:11273-80.
Latorre R, Sternini C, De Giorgio R, Greenwood-Van Meerveld B. Enteroendocrine cells: a review of their role in brain-gut communication. Neurogastroenterol Motil 2016;28:620-30.
Middelhoff M, Westphalen CB, Hayakawa Y, Yan KS, Gershon MD, Wang TC, et al. Dclk1-expressing tuft cells: critical modulators of the intestinal niche? Am J Physiol Gastrointest Liver Physiol 2017;313:G285-99.
Van Landeghem L, Chevalier J, Mahe MM, Wedel T, Urvil P, Derkinderen P, et al. Enteric glia promote intestinal mucosal healing via activation of focal adhesion kinase and release of proEGF. Am J Physiol Gastrointest Liver Physiol 2011;300:G976-87.
Grundmann D, Loris E, Maas-Omlor S, Huang W, Scheller A, Kirchhoff F, et al. Enteric glia: S100, GFAP, and beyond. Anat Rec (Hoboken) 2019;302:1333-44.
Grubisic V, Gulbransen BD. Enteric glia: the most alimentary of all glia. J Physiol 2017;595:557-70.
Fornai M, van den Wijngaard RM, Antonioli L, Pellegrini C, Blandizzi C, de Jonge WJ. Neuronal regulation of intestinal immune functions in health and disease. Neurogastroenterol Motil 2018;30:e13406.
Meir M, Kannapin F, Diefenbacher M, Ghoreishi Y, Kollmann C, Flemming S, et al. Intestinal epithelial barrier maturation by enteric glial cells is GDNF-dependent. Int J Mol Sci 2021;22:1887.
Braak H, Rub U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 2003;110:517-36.
von Boyen GB, Schulte N, Pfluger C, Spaniol U, Hartmann C, Steinkamp M. Distribution of enteric glia and GDNF during gut inflammation. BMC Gastroenterol 2011;11:3.
Del Tredici K, Braak H. Review: Sporadic Parkinson's disease: development and distribution of alpha-synuclein pathology. Neuropathol Appl Neurobiol 2016;42:33-50.
How to Cite
Casini, A., Mancinelli, R., Mammola, C. L., Pannarale, L., Chirletti, P., Onori, P., & Vaccaro, R. (2021). Distribution of alpha-synuclein in normal human jejunum and its relations with the chemosensory and neuroendocrine system. European Journal of Histochemistry, 65(4). https://doi.org/10.4081/ejh.2021.3310
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Li Wu, Dan Han, Jie Jiang, Xiaojie Xie, Xunran Zhao, Tengfei Ke, Wen Zhao, Liu Liu, Wei Zhao, Co-transplantation of bone marrow mesenchymal stem cells and monocytes in the brain stem to repair the facial nerve axotomy , European Journal of Histochemistry: Vol. 64 No. s2 (2020): Special Collection on Stem Cells and Regenerative Medicine
- S Preziuso, E Sanna, MP Sanna, C Loddo, D Cerri, E Taccini, F Mariotti, G Braca, G Rossi, Association of Maedi Visna virus with Brucella ovis infection in rams , European Journal of Histochemistry: Vol. 47 No. 2 (2003)
- Carolina dos Santos Jacob, Gabriela Klein Barbosa, Mariana Pasquini Rodrigues, Jurandyr Pimentel Neto, Lara Caetano Rocha, Adriano Polican Ciena, Stretching prior to resistance training promotes adaptations on the postsynaptic region in different myofiber types , European Journal of Histochemistry: Vol. 66 No. 1 (2022)
- C Demonceau, AS Marshall, J Sales, E Heinen, Investigation of close interactions between sympathetic neural fibres and the follicular dendritic cells network in the mouse spleen , European Journal of Histochemistry: Vol. 52 No. 2 (2008)
- G. Orsini, A. Majorana, A. Mazzoni, A. Putignano, M. Falconi, A. Polimeni, L. Breschi, Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta , European Journal of Histochemistry: Vol. 58 No. 4 (2014)
- B. Bloch, Molecular anatomy of neuronal interactions with special reference to the dopamine control of striatal functions , European Journal of Histochemistry: Vol. 46 No. 4 (2002)
- G Pons, V Evangelisti, F Caprì, S Mozzone, A Viarengo, Cytochemical localization and quantification of plasma membrane Ca2+-ATPase activity in mollusc digestive gland cells , European Journal of Histochemistry: Vol. 46 No. 1 (2002)
- E Sanna, MP Sanna, C Loddo, Endogenous Jaagsiekte Sheep Retrovirus RNA is expressed by different cell types in ovine foetus and placenta , European Journal of Histochemistry: Vol. 46 No. 3 (2002)
- G Tuccari, G Giuffrè, R Scarfì, A Simone, P Todaro, G Barresi, Immunolocalization of lactoferrin in surgically resected pigmented skin lesions , European Journal of Histochemistry: Vol. 49 No. 1 (2005)
- Shufeng Xiao, Haoren Tang, Yao Bai, Renchao Zou, Zongfang Ren, Xuesong Wu, Zhitian Shi, Song Lan, Wei Liu, Tiangen Wu, Cheng Zhang, Lin Wang, Swertiamarin suppresses proliferation, migration, and invasion of hepatocellular carcinoma cells via negative regulation of FRAT1 , European Journal of Histochemistry: Vol. 64 No. 4 (2020)
<< < 59 60 61 62 63 64 65 66 67 68 > >>
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
2
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
94
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
