title: Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system.
abstract: OBJECTIVE
  Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus.
  
  
  METHODS
  Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin.
  
  
  RESULTS
  a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS.
  
  
  CONCLUSIONS
  The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age.
authors.affiliation: Department of Anatomy, Christian Albrecht´s University, Kiel, Germany. Electronic address: m.boettner@anat.uni-kiel.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Böttner
authors.affiliation: Department of Anatomy, Christian Albrecht´s University, Kiel, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Fricke
authors.affiliation: Department of Anatomy, Christian Albrecht´s University, Kiel, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Anatomy, Christian Albrecht´s University, Kiel, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Barrenschee
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
authors.affiliation: Department of General, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Egberts
authors.affiliation: Department of General, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Fritscher-Ravens
authors.affiliation: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Ellrichmann
authors.affiliation: Prion and Dementia Research Unit, Institute of Neuropathology, University of Goettingen, Germany.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Schulz-Schaeffer
authors.affiliation: Department of Anatomy, Christian Albrecht´s University, Kiel, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Wedel
mesh_terms: D000367:Age Factors; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018709:Statistics, Nonparametric; D013572:Synaptic Vesicles / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016708:Synaptophysin; C482860:UCHL1 protein, human; D051844:alpha-Synuclein; D043222:Ubiquitin Thiolesterase
keywords: Alpha synuclein; Enteric nerve cell culture; Enteric nervous system; Human colon; Synaptic vesicles