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Neurobiol Dis. 2012 Dec;48(3):474-80. doi: 10.1016/j.nbd.2012.07.018. Epub 2012 Jul 28.

Expression pattern and localization of alpha-synuclein in the human enteric nervous system.

Author information

1
Department of Anatomy, Christian Albrecht's University, and Department of Neurology, University Hospital Schleswig-Holstein, Otto-Hahn-Platz 8, 24118 Kiel, Germany. m.boettner@anat.uni-kiel.de

Abstract

BACKGROUND:

Alpha-synuclein (α-syn) is abundantly expressed in the central nervous system and involved in the regulation of neurotransmission. Insoluble fibrils of phosphorylated α-synuclein (p-α-syn) have been implicated in several neurodegenerative diseases (e.g. Parkinson's disease, Alzheimer's disease). The aim of the study was to determine the gene expression pattern and localization of α-syn/p-α-syn in the human enteric nervous system (ENS).

METHODS:

Human colonic specimens (n=13, 15-83 years) were processed for α-syn and p-α-syn immunohistochemistry. Colocalization of α-syn was assessed by dual-labeling with pan-neuronal markers (PGP 9.5, HuC/D). For qPCR studies, tissue was obtained from full-thickness sections, tunica muscularis, submucosa, mucosa, and laser-microdissected (LMD) enteric ganglia.

RESULTS:

Highest α-syn levels were detectable within the tunica muscularis and submucosa. Ganglia isolated by LMD showed high expression of α-syn mRNA. All myenteric and submucosal ganglia and nerve fibers were immunoreactive for α-syn. Dual-labeling revealed colocalization of α-syn with both pan-neuronal markers. p-α-syn immunoreactivity was consistently observed in specimens from adults with increasing age.

CONCLUSIONS:

α-syn is abundantly expressed in all nerve plexus of the human ENS including both neuronal somata and processes. The presence of p-α-syn within the ENS is a regular finding in adults with increasing age and may not be regarded as pathological correlate. The data provide a basis to unravel the functions of α-syn and to evaluate altered α-syn in enteric neuropathies and α-synucleinopathies of the CNS with gastrointestinal manifestations.

PMID:
22850485
DOI:
10.1016/j.nbd.2012.07.018
[Indexed for MEDLINE]

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