title: Expression pattern and localization of alpha-synuclein in the human enteric nervous system.
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.
authors: 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
authors: Martina
authors: M
authors: Böttner
authors: Dimitri
authors: D
authors: Zorenkov
authors: Ines
authors: I
authors: Hellwig
authors: Martina
authors: M
authors: Barrenschee
authors: Jonas
authors: J
authors: Harde
authors: Tobias
authors: T
authors: Fricke
authors: Günther
authors: G
authors: Deuschl
authors: Jan-Hendrik
authors: JH
authors: Egberts
authors: Thomas
authors: T
authors: Becker
authors: Annette
authors: A
authors: Fritscher-Ravens
authors: Alexander
authors: A
authors: Arlt
authors: Thilo
authors: T
authors: Wedel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017615:Enteric Nervous System / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D055815:Young Adult; D051844:alpha-Synuclein / Q000032:analysis* / Q000096:biosynthesis*
chemical_list: D051844:alpha-Synuclein