Distribution of α-synuclein in Normal Human Jejunum and Its Relations with the Chemosensory and Neuroendocrine System

Overview

Journal Eur J Histochem

Specialty Biochemistry

Date 2021 Nov 2

PMID 34726359

Citations 7

Authors

Arianna Casini

Romina Mancinelli

Caterina Loredana Mammola

Luigi Pannarale

Piero Chirletti

Paolo Onori

Rosa Vaccaro

Affiliations

Soon will be listed here.

Abstract

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.

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References

Resnikoff H, Metzger J, Lopez M, Bondarenko V, Mejia A, Simmons H . Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates. J Inflamm Res. 2019; 12:113-126. PMC: 6511240. DOI: 10.2147/JIR.S196552. View

Grubisic V, Gulbransen B . Enteric glia: the most alimentary of all glia. J Physiol. 2016; 595(2):557-570. PMC: 5233670. DOI: 10.1113/JP271021. View

Larsen K, Schmitz Y, Troyer M, Mosharov E, Dietrich P, Quazi A . Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci. 2006; 26(46):11915-22. PMC: 6674868. DOI: 10.1523/JNEUROSCI.3821-06.2006. View

Lema I, Araujo J, Rolhion N, Demignot S . Jejunum: The understudied meeting place of dietary lipids and the microbiota. Biochimie. 2020; 178:124-136. DOI: 10.1016/j.biochi.2020.09.007. View

Del Colle A, Israelyan N, Margolis K . Novel aspects of enteric serotonergic signaling in health and brain-gut disease. Am J Physiol Gastrointest Liver Physiol. 2019; 318(1):G130-G143. PMC: 6985840. DOI: 10.1152/ajpgi.00173.2019. View

Pouclet H, Lebouvier T, Coron E, Rouaud T, Flamant M, Toulgoat F . Analysis of colonic alpha-synuclein pathology in multiple system atrophy. Parkinsonism Relat Disord. 2012; 18(7):893-5. DOI: 10.1016/j.parkreldis.2012.04.020. View

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(9):416-22. DOI: 10.1038/ncpgasthep0259. View

Meir M, Kannapin F, Diefenbacher M, Ghoreishi Y, Kollmann C, Flemming S . Intestinal Epithelial Barrier Maturation by Enteric Glial Cells Is GDNF-Dependent. Int J Mol Sci. 2021; 22(4). PMC: 7917776. DOI: 10.3390/ijms22041887. View

Martin L, Pan Y, Price A, Sterling W, Copeland N, Jenkins N . Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci. 2006; 26(1):41-50. PMC: 6381830. DOI: 10.1523/JNEUROSCI.4308-05.2006. View

10.

Sbarbati A, Crescimanno C, Benati D, Osculati F . Solitary chemosensory cells in the developing chemoreceptorial epithelium of the vallate papilla. J Neurocytol. 1999; 27(9):631-5. DOI: 10.1023/a:1006933528084. View

11.

Scholz S, Houlden H, Schulte C, Sharma M, Li A, Berg D . SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol. 2009; 65(5):610-4. PMC: 3520128. DOI: 10.1002/ana.21685. View

12.

Ronnestad I, Akiba Y, Kaji I, Kaunitz J . Duodenal luminal nutrient sensing. Curr Opin Pharmacol. 2014; 19:67-75. PMC: 4845631. DOI: 10.1016/j.coph.2014.07.010. View

13.

Schneider C, OLeary C, Locksley R . Regulation of immune responses by tuft cells. Nat Rev Immunol. 2019; 19(9):584-593. PMC: 8331098. DOI: 10.1038/s41577-019-0176-x. View

14.

Koo A, Fothergill L, Kuramoto H, Furness J . 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(6):623-636. DOI: 10.1007/s00418-021-01972-3. View

15.

Diwakarla S, Fothergill L, Fakhry J, Callaghan B, Furness J . Heterogeneity of enterochromaffin cells within the gastrointestinal tract. Neurogastroenterol Motil. 2017; 29(6). PMC: 5475263. DOI: 10.1111/nmo.13101. View

16.

Braak H, de Vos R, 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. 2005; 396(1):67-72. DOI: 10.1016/j.neulet.2005.11.012. View

17.

Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Bjorklund T . Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014; 128(6):805-20. DOI: 10.1007/s00401-014-1343-6. View

18.

Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S . TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci U S A. 2009; 106(9):3408-13. PMC: 2651261. DOI: 10.1073/pnas.0805323106. View

19.

Fornai M, van den Wijngaard R, Antonioli L, Pellegrini C, Blandizzi C, de Jonge W . Neuronal regulation of intestinal immune functions in health and disease. Neurogastroenterol Motil. 2018; 30(12):e13406. DOI: 10.1111/nmo.13406. View

20.

Del Tredici K, Braak H . Review: Sporadic Parkinson's disease: development and distribution of α-synuclein pathology. Neuropathol Appl Neurobiol. 2015; 42(1):33-50. DOI: 10.1111/nan.12298. View